HIF-1 α as a central mediator of cellular resistance to intracellular pathogens.
HIF-1α as a central mediator of cellular resistance to intracellular pathogens. Curr Opin Immunol. 2019 Jun 20;60:111-116 Authors: Knight M, Stanley S Abstract Hypoxia-inducible transcription factor-1α (HIF-1α) was originally identified as a master regulator of cellular responses to hypoxia. More recently, HIF-1α has emerged as a critical regulator of immune cell function that couples shifts in cellular metabolism to cell type-specific transcriptional outputs. Activation of macrophages with inflammatory stimuli leads to induction of the metabolic program aerobic glycolysis and ...
Source: Current Opinion in Immunology - June 20, 2019 Category: Allergy & Immunology Authors: Knight M, Stanley S Tags: Curr Opin Immunol Source Type: research

Apoptosis inhibition by intracellular bacteria and its consequence on host immunity.
Abstract Regulated cell death via apoptosis not only is important for organismal homeostasis but also serves as an innate defense mechanism. The engulfment of apoptotic infected cells, a process known as efferocytosis, is a common pathway for the destruction of many intracellular bacteria. Some pathogens take advantage of efferocytosis to prevent activation of macrophages and thereby facilitate their dissemination. Conversely, many obligate intracellular bacterial pathogens and some facultative-intracellular bacteria inhibit apoptosis, preventing efferocytosis, and evading innate host defenses. The molecular mecha...
Source: Current Opinion in Immunology - June 19, 2019 Category: Allergy & Immunology Authors: Behar SM, Briken V Tags: Curr Opin Immunol Source Type: research

Reactive nitrogen species in host-bacterial interactions.
res A Abstract Reactive nitrogen species play diverse and essential roles in host-pathogen interactions. Here, we review selected recent discoveries regarding nitric oxide (NO) in host defense and the pathogenesis of infection, mechanisms of bacterial NO resistance, production of NO by human macrophages, NO-based antimicrobial therapeutics and NO interactions with the gut microbiota. PMID: 31200187 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - June 11, 2019 Category: Allergy & Immunology Authors: Fang FC, Vázquez-Torres A Tags: Curr Opin Immunol Source Type: research

Contribution of antimicrobials to the development of allergic disease.
Abstract Antimicrobials represent a broad class of chemicals with the intended purpose of eliminating or controlling the growth of harmful microorganisms. Exposure can occur occupationally or through the use or consumption of consumer products. The use of antimicrobial agents has been associated with an increased incidence of allergic diseases, including asthma, atopic dermatitis, and less commonly, anaphylaxis. Very diverse immunological mechanisms and mediators have been identified in the sensitization response to antimicrobial chemicals and the importance of the local microenviroment in the response is increasi...
Source: Current Opinion in Immunology - June 8, 2019 Category: Allergy & Immunology Authors: Anderson SE, Weatherly L, Shane HL Tags: Curr Opin Immunol Source Type: research

Heterogeneity and fate choice: T cell exhaustion in cancer and chronic infections.
Abstract CD8 T cell differentiation is a tightly regulated process generating effector and memory T cells over the course of acute infections. In cancer and chronic infection, this differentiation program is derailed, and antigen-specific CD8 T cells differentiate to a hyporesponsive state generally referred to as T cell exhaustion. Here, we review recent findings on heterogeneity of tumor-specific T cells and exhausted T cells during chronic infections, discussing distinct differentiation state dynamics, fate choices, and functional states. Delineating the regulatory mechanisms defining distinct T cell states and...
Source: Current Opinion in Immunology - June 7, 2019 Category: Allergy & Immunology Authors: Philip M, Schietinger A Tags: Curr Opin Immunol Source Type: research

Cell-autonomous immunity by IFN-induced GBPs in animals and plants.
Abstract Inside host cells, guanylate binding proteins (GBPs) rapidly assemble into large antimicrobial defense complexes that combat a wide variety of bacterial pathogens. These massive nanomachines often completely coat targeted microbes where they act as recruitment platforms for downstream effectors capable of direct bactericidal activity. GBP-containing platforms also serve as sensory hubs to activate inflammasome-driven responses in the mammalian cytosol while in plants like Arabidopsis, GBP orthologues may facilitate intranuclear signaling for immunity against invasive phytopathogens. Together, this group o...
Source: Current Opinion in Immunology - June 5, 2019 Category: Allergy & Immunology Authors: Huang S, Meng Q, Maminska A, MacMicking JD Tags: Curr Opin Immunol Source Type: research

Host inflammasome defense mechanisms and bacterial pathogen evasion strategies.
Abstract Inflammasomes are a formidable armada of intracellular pattern recognition receptors. They recognize determinants of infection, such as foreign entities or danger signals within the host cell cytosol, rapidly executing innate immune defenses and initiating adaptive immune responses. Although inflammasomes are implicated in many diseases, they are especially critical in host protection against intracellular bacterial pathogens. Given this role, it is not surprising that many pathogens have evolved effective strategies to evade inflammasome activation. In this review, we will provide a brief summary of infl...
Source: Current Opinion in Immunology - June 4, 2019 Category: Allergy & Immunology Authors: Brewer SM, Brubaker SW, Monack DM Tags: Curr Opin Immunol Source Type: research

Remembering to remember: T cell memory maintenance and plasticity.
Abstract Upon activation, naive T cells give rise to a heterogeneous cell population of effector and memory T cells that mediate antigen clearance and provide long-lived protection from rechallenge. Many of the transcriptional regulators that direct the differentiation of naive T cells to acquire the range of phenotypic and functional characteristics of effector and memory T cells have been described. However, the active programs that maintain the specific subsets of memory T cells are less clear. Here, we discuss recent studies that suggest effector and memory CD8+ T cells exist in cellular 'states' with inherent...
Source: Current Opinion in Immunology - June 3, 2019 Category: Allergy & Immunology Authors: Omilusik KD, Goldrath AW Tags: Curr Opin Immunol Source Type: research

Genetic evidence for the role of transforming growth factor- β in atopic phenotypes.
Genetic evidence for the role of transforming growth factor-β in atopic phenotypes. Curr Opin Immunol. 2019 Jun 01;60:54-62 Authors: Weissler KA, Frischmeyer-Guerrerio PA Abstract New evidence in humans and mice supports a role for transforming growth factor-β (TGF-β) in the initiation and effector phases of allergic disease, as well as in consequent tissue dysfunction. This pleiotropic cytokine can affect T cell activation and differentiation and B cell immunoglobulin class switching following initial encounter with an allergen. TGF-β can also act on mast cells during an acute all...
Source: Current Opinion in Immunology - June 1, 2019 Category: Allergy & Immunology Authors: Weissler KA, Frischmeyer-Guerrerio PA Tags: Curr Opin Immunol Source Type: research

Development, ontogeny, and maintenance of TCR αβ+ CD8αα IEL.
Development, ontogeny, and maintenance of TCRαβ+ CD8αα IEL. Curr Opin Immunol. 2019 May 27;58:83-88 Authors: Ruscher R, Hogquist KA Abstract The intestinal epithelium is the outermost cellular layer that separates the body from the gut lumen. The integrity of this protective mucosal barrier is crucial and maintained by specialized cells-intraepithelial lymphocytes (IEL). Much research has been conducted on these cells and our overall understanding of them is increasing rapidly. In this review we focus on the TCRαβ+ subset of CD8αα IEL. We discuss recent st...
Source: Current Opinion in Immunology - May 27, 2019 Category: Allergy & Immunology Authors: Ruscher R, Hogquist KA Tags: Curr Opin Immunol Source Type: research

MAIT cells: programmed in the thymus to mediate immunity within tissues.
Abstract MAIT cells are an evolutionarily conserved T cell subset recognizing ubiquitous microbial metabolites. Herein, we review recent literature showing that MAIT cells can be divided into type 1 and type 17 subsets, which acquire a tissue resident differentiation program in the thymus and localize in specific tissues. We also discuss the nature and in vivo availability of the different agonist and antagonist MAIT ligands with potential consequences for MAIT cell biology. PMID: 31141764 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - May 26, 2019 Category: Allergy & Immunology Authors: Lantz O, Legoux F Tags: Curr Opin Immunol Source Type: research

New players in the gene regulatory network controlling late B cell differentiation.
Abstract The differentiation of B cells into antibody-secreting plasma cells is associated with profound changes in morphology, lifespan, and cellular metabolism that are needed to support high rates of antibody production. These processes are driven by dramatic alterations to the transcriptional program and to the organization of the nucleus itself that in turn are regulated by the activity of a select group of transcription factors and epigenetic regulators. Although the core differentiation program is conserved in all mature B cells, subset-specific regulators, such as those found in B1 or memory B cells, provi...
Source: Current Opinion in Immunology - May 24, 2019 Category: Allergy & Immunology Authors: Willis SN, Nutt SL Tags: Curr Opin Immunol Source Type: research

Role of genetics, environment, and their interactions in the pathogenesis of eosinophilic esophagitis.
Abstract The rise in incidence and prevalence of eosinophilic esophagitis (EoE) since the 1990s has prompted investigations into its pathogenesis, natural history, and management. Identified genetic variants in FLG, DSG1, CAPN14, SPINK5, and SPINK7 link EoE to epithelial barrier dysfunction, whereas variants in CCL26, POSTN, and TSLP associate EoE with T helper type 2-mediated immunity. Early-life, infectious, and geographic factors have been implicated in promoting esophageal microbial dysbiosis and, subsequently, T helper type 2 immune responses. However, research into environmental factors and their interaction...
Source: Current Opinion in Immunology - May 24, 2019 Category: Allergy & Immunology Authors: Lyles J, Rothenberg M Tags: Curr Opin Immunol Source Type: research

γδTCR-independent origin of neonatal γδ T cells prewired for IL-17 production.
γδTCR-independent origin of neonatal γδ T cells prewired for IL-17 production. Curr Opin Immunol. 2019 May 22;58:60-67 Authors: Spidale NA, Frascoli M, Kang J Abstract A classical view of T cell lineages consists of two major clades of T cells expressing either the αβ or γδ T cell receptor (TCR). However, genome-wide assessments indicate molecular clusters segregating T cell subsets that are preprogrammed for effector function (innate) from those that mediate conventional adaptive response, regardless of the TCR types. Within this paradigm, γδ...
Source: Current Opinion in Immunology - May 22, 2019 Category: Allergy & Immunology Authors: Spidale NA, Frascoli M, Kang J Tags: Curr Opin Immunol Source Type: research

Parallel worlds of the adaptive and innate immune cell networks.
Abstract Adaptive and innate immune cells have typically been functionally and temporally segregated even though they share a number of salient features. Over the past decade, significant advances have been made in understanding the composition and diversity of both innate and adaptive cell populations. This has shed light on how cells from two distinct pathways are so highly complementary. Innate lymphoid cells (ILCs) are pivotally positioned in tissues to form a stable population akin to tissue-resident T cells that protects the body. Nevertheless, the pathway by which different lymphocytes enter tissues, termin...
Source: Current Opinion in Immunology - May 20, 2019 Category: Allergy & Immunology Authors: Huang Q, Belz GT Tags: Curr Opin Immunol Source Type: research

Human inborn errors of immunity to infection affecting cells other than leukocytes: from the immune system to the whole organism.
Abstract Studies of vertebrate immunity have traditionally focused on professional cells, including circulating and tissue-resident leukocytes. Evidence that non-professional cells are also intrinsically essential (i.e. not via their effect on leukocytes) for protective immunity in natural conditions of infection has emerged from three lines of research in human genetics. First, studies of Mendelian resistance to infection have revealed an essential role of DARC-expressing erythrocytes in protection against Plasmodium vivax infection, and an essential role of FUT2-expressing intestinal epithelial cells for protect...
Source: Current Opinion in Immunology - May 20, 2019 Category: Allergy & Immunology Authors: Zhang SY, Jouanguy E, Zhang Q, Abel L, Puel A, Casanova JL Tags: Curr Opin Immunol Source Type: research

The NLRP1 inflammasome: new mechanistic insights and unresolved mysteries.
Abstract Nucleotide-binding domain, leucine-rich repeat (NLR) proteins constitute a diverse class of innate immune sensors that detect pathogens or stress-associated stimuli in plants and animals. Some NLRs are activated upon direct binding to pathogen-derived ligands. In contrast, we focus here on a vertebrate NLR called NLRP1 that responds to the enzymatic activities of pathogen effectors. We discuss a newly proposed 'functional degradation' mechanism that explains activation and assembly of NLRP1 into an oligomeric complex called an inflammasome. We also discuss how NLRP1 is activated by non-pathogen-associated...
Source: Current Opinion in Immunology - May 20, 2019 Category: Allergy & Immunology Authors: Mitchell PS, Sandstrom A, Vance RE Tags: Curr Opin Immunol Source Type: research

Role of neurons in the control of immune defense.
Abstract Studies in recent years have strengthened the notion that neural mechanisms are involved in the control of immune responses. From initial studies that highlighted the vagus nerve control of inflammatory responses in vertebrates, many advances have been made, including the dissection of specific neural circuits that are involved in controlling immunity. Part of this has been facilitated by the use of a tractable model animal, Caenorhabditis elegans, in which individual neurons involved in sensing pathogens and controlling the immune response have been identified. Importantly, some of the underlying mechani...
Source: Current Opinion in Immunology - May 19, 2019 Category: Allergy & Immunology Authors: Hoffman C, Aballay A Tags: Curr Opin Immunol Source Type: research

Granulysin: killer lymphocyte safeguard against microbes.
Abstract Primary T cell immunodeficiency and HIV-infected patients are plagued by non-viral infections caused by bacteria, fungi, and parasites, suggesting an important and underappreciated role for T lymphocytes in controlling microbes. Here, we review recent studies showing that killer lymphocytes use the antimicrobial cytotoxic granule pore-forming peptide granulysin, induced by microbial exposure, to permeabilize cholesterol-poor microbial membranes and deliver death-inducing granzymes into these pathogens. Granulysin and granzymes cause microptosis, programmed cell death in microbes, by inducing reactive oxyg...
Source: Current Opinion in Immunology - May 18, 2019 Category: Allergy & Immunology Authors: Dotiwala F, Lieberman J Tags: Curr Opin Immunol Source Type: research

The microbiome: toward preventing allergies and asthma by nutritional intervention.
Abstract Allergies and asthma have increased in prevalence over recent decades while the development of therapies to treat or prevent them has stagnated. Genetic predisposition and lifestyle changes influence the constituents of the microbiome and these host-environment-microbe interactions represent a key underlying pressure influencing disease susceptibility. Consequently, there has been a surge of interest in shaping the microbiome to a health-promoting state particularly through nutritional intervention strategies. However, mechanistic insights into the nutrition-microbe-host interplay are still needed in orde...
Source: Current Opinion in Immunology - May 8, 2019 Category: Allergy & Immunology Authors: Perdijk O, Marsland BJ Tags: Curr Opin Immunol Source Type: research

Pertussis vaccines and protective immunity.
Abstract Despite high vaccine coverage, reported cases of pertussis have increased steadily over the last twenty years. This resurgence has stimulated interest in host responses to pertussis infection and vaccination with the goal of developing more effective next-generation vaccines and vaccination strategies. Optimal protection against Bordetella pertussis appears to be multifactorial requiring both humoral and cellular responses. Natural infection and whole-cell pertussis vaccination induce Th1 and Th17-dominated responses. In contrast, acellular vaccines induce Th2-dominated responses. Available immunological ...
Source: Current Opinion in Immunology - May 8, 2019 Category: Allergy & Immunology Authors: Kapil P, Merkel TJ Tags: Curr Opin Immunol Source Type: research

NextGen cell-based immunotherapies in cancer and other immune disorders.
Abstract T lymphocyte and other cell therapies have the potential to transform how we treat cancers and other diseases that have few therapeutic options. Here, we review the current progress in engineered T cell therapies and look to the future of what will establish cell therapy as the next pillar of medicine. The tools of synthetic biology along with fundamental knowledge in cell biology and immunology have enabled the development of approaches to engineer cells with enhanced capacity to recognize and treat disease safely and effectively. This along with new modes of engineering cells with CRISPR and strategies ...
Source: Current Opinion in Immunology - May 6, 2019 Category: Allergy & Immunology Authors: Azimi CS, Tang Q, Roybal KT, Bluestone JA Tags: Curr Opin Immunol Source Type: research

Antigen presentation by dendritic cells for B cell activation.
Abstract B cells are efficiently activated by antigens presented on cell membranes, which provide opportunity for receptor cross-linking and antigen capture. The two main cell types implicated in native antigen presentation to B cells are follicular dendritic cells (FDC), which reside in B cell follicles, and CD169+ macrophages, which line the antigen-exposed surfaces of these follicles in both the lymph nodes and the spleen. There is mounting evidence, however, that conventional dendritic cells (cDC) can also participate in native antigen presentation to B cells. This underappreciated role, largely hidden by the ...
Source: Current Opinion in Immunology - May 6, 2019 Category: Allergy & Immunology Authors: Heath WR, Kato Y, Steiner TM, Caminschi I Tags: Curr Opin Immunol Source Type: research

MARCH ligases in immunity.
Abstract Membrane associated RING-CH (MARCH) ubiquitin ligases control the stability, trafficking and function of important immunoreceptors, including MHC molecules and costimulatory molecule CD86. Regulation of the critical antigen presenting molecule MHC II by MARCH1 and the control of MARCH1 expression by inflammatory stimuli is a key step in the function of antigen presenting cells. MHC II ubiquitination by MARCH8 and CD83 plays a critical role in T cell thymic selection. Recent studies reveal new immune functions of MARCH ligases in innate immunity, regulation of FcγR expression and Treg development. In...
Source: Current Opinion in Immunology - May 4, 2019 Category: Allergy & Immunology Authors: Liu H, Mintern JD, Villadangos JA Tags: Curr Opin Immunol Source Type: research

Metals as phagocyte antimicrobial effectors.
Abstract Transition metal ions are essential to bacterial pathogens and their hosts alike but are harmful in excess. In an effort to curtail the replication of intracellular bacteria, host phagocytes exploit both the essentiality and toxicity of transition metals. In the paradigmatic description of nutritional immunity, iron and manganese are withheld from phagosomes to starve microbial invaders of these nutrients. Conversely, the destructive properties of copper and zinc appear to be harnessed by phagocytes, where these metals are delivered in excess to phagosomes to intoxicate internalized bacteria. Here, we bri...
Source: Current Opinion in Immunology - May 4, 2019 Category: Allergy & Immunology Authors: Sheldon JR, Skaar EP Tags: Curr Opin Immunol Source Type: research

Protein engineering and particulate display of B-cell epitopes to facilitate development of novel vaccines.
Abstract Induction of antigen-specific humoral immunity is a correlate of protection for many diseases and remains a primary vaccine goal. Pathogens can evade such responses by limiting epitope access, by diversifying surface residues, or by keeping antigens in metastable conformations. B cells can target diverse epitopes on an antigen, but only a subset of which produce functional antibodies. Structure-based immunogen engineering can help overcome these hurdles by using structural information for targeted induction of particular antibodies while improving the overall vaccine immunogenicity. This review will cover...
Source: Current Opinion in Immunology - April 25, 2019 Category: Allergy & Immunology Authors: Xu Z, Kulp DW Tags: Curr Opin Immunol Source Type: research

High-affinity anti-glycan antibodies: challenges and strategies.
Abstract High-affinity binding of antibodies provides for increased specificity and usually higher effector functions in vivo. This goal, well documented in cancer immunotherapy, is very relevant to vaccines as well, and has particularly significant application toward glycan antigens. The inability to elicit high-affinity antibodies has limited potential applications of glycan-based immunogens, giving rise to insufficient population coverage due to low titers and short duration of protection. That such vaccines have achieved widespread use in spite of these shortcomings highlights the surpassing importance of glyc...
Source: Current Opinion in Immunology - April 25, 2019 Category: Allergy & Immunology Authors: Polonskaya Z, Savage PB, Finn MG, Teyton L Tags: Curr Opin Immunol Source Type: research

Immunological goals for respiratory syncytial virus vaccine development.
Abstract Defining the immunological goals for respiratory syncytial virus (RSV) vaccination requires understanding of RSV biology and tropism, mechanisms of cell-to-cell spread and immunity, epidemiology, and transmission dynamics. The immunological goals for a particular vaccine would be product-specific based on antigen selection, delivery approach, and target population. There are many ways to achieve immunity against RSV infection involving innate and adaptive responses, humoral, and cellular effector mechanisms, and mucosal and systemic responses. Both protective and pathological immune response patterns have...
Source: Current Opinion in Immunology - April 24, 2019 Category: Allergy & Immunology Authors: Graham BS Tags: Curr Opin Immunol Source Type: research

Understanding the immunology of Shingrix, a recombinant glycoprotein E adjuvanted herpes zoster vaccine.
Abstract Herpes zoster is common in older and immune suppressed persons due to diminished VZV-specific cellular immunity. A recombinant herpes zoster vaccine (RZV) consisting of a single VZV glycoprotein and an adjuvant system stimulates robust and persistent VZV-specific antibody and CD4+ T cell responses in these high-risk populations. VZV-specific immune responses induced by RZV, including the generation of polyfunctional T cells, are driven by the synergistic actions of the components of the vaccine adjuvant system. RZV provides unprecedented protection against herpes zoster in older adults regardless of age a...
Source: Current Opinion in Immunology - April 16, 2019 Category: Allergy & Immunology Authors: Heineman TC, Cunningham A, Levin M Tags: Curr Opin Immunol Source Type: research

Innate sensors that regulate vaccine responses.
Abstract Pattern recognition receptors (PRRs) control elemental functions of antigen presenting cells (APCs) and critically shape adaptive immune responses. Wielding a natural adjuvanticity, live attenuated vaccines elicit exceptionally efficient and durable immunity. Commonly used vaccine adjuvants target individual PRRs or bolster the immunogenicity of vaccines via indirect mechanisms of inflammation. Here, we review the impact of innate sensors on immune responses to live attenuated vaccines and commonly used vaccine adjuvants, with a focus on human vaccine responses. We discuss the unique potential of microbia...
Source: Current Opinion in Immunology - April 9, 2019 Category: Allergy & Immunology Authors: Georg P, Sander LE Tags: Curr Opin Immunol Source Type: research

Understanding the immunology of the Zostavax shingles vaccine.
Abstract Zostavax is a live-attenuated varicella zoster virus (VZV) vaccine recommended for use in adults>50 years of age to prevent shingles. The main risk factor for the development of shingles is age, which correlates with decreasing cell-mediated immunity. These data suggest a predominant role of T cell immunity in controlling VZV latency. However, other components of the immune system may also contribute. In this review, we will discuss how the immune system responds to Zostavax, focusing on recent studies examining innate immunity, transcriptomics, metabolomics, cellular, and humoral immunity. PMID: ...
Source: Current Opinion in Immunology - April 7, 2019 Category: Allergy & Immunology Authors: Sullivan NL, Eberhardt CS, Wieland A, Vora KA, Pulendran B, Ahmed R Tags: Curr Opin Immunol Source Type: research

Vaccination against atherosclerosis.
Abstract Atherosclerosis is a chronic inflammatory disease that causes most heart attacks and strokes, making it the biggest killer in the world. Although cholesterol-lowering drugs have dramatically reduced these major adverse cardiovascular events, there remains a high residual risk called inflammatory risk. Atherosclerosis has an autoimmune component that can be manipulated by immunologic approaches including vaccination. Vaccination is attractive, because it is antigen-specific, does not impair host defense, and provides long-term protection. Several candidate antigens for atherosclerosis vaccine development h...
Source: Current Opinion in Immunology - March 28, 2019 Category: Allergy & Immunology Authors: Kobiyama K, Saigusa R, Ley K Tags: Curr Opin Immunol Source Type: research

Tfh cell response in influenza vaccines in humans: what is visible and what is invisible.
Abstract Elucidating the immune mechanism by which seasonal influenza vaccines induce a protective immune response is of great importance to gain insights into the design of next-generation vaccines conferring more effective and long-lasting immune protection. Recent studies have established that T follicular helper (Tfh) cells play a major role for the generation of antibody response following influenza vaccination. Yet, the evidence is gained largely through the analysis of blood samples, and our knowledge on the role of Tfh cells in influenza vaccination is still largely limited to the generation of antigen-spe...
Source: Current Opinion in Immunology - March 25, 2019 Category: Allergy & Immunology Authors: Ueno H Tags: Curr Opin Immunol Source Type: research

Mitochondrial antigen presentation: a mechanism linking Parkinson's disease to autoimmunity.
Abstract Parkinson's disease (PD) is caused by the progressive loss of dopaminergic neurons and afflicts millions of people world-wide. The current treatments address only the late motor symptoms, with no cure or preventive therapeutic approaches. The contribution of dysfunctional immune mechanisms in PD has been clearly established, with an emphasis on neuroinflammation and microglial cell activation. Recent studies have widened the involvement of the immune system in this disease by clearly showing the engagement of adaptive immunity and antigen presentation processes, directly regulated by PD-related proteins, ...
Source: Current Opinion in Immunology - March 21, 2019 Category: Allergy & Immunology Authors: Fahmy AM, Boulais J, Desjardins M, Matheoud D Tags: Curr Opin Immunol Source Type: research

Antigenic cross-reactivity between Zika and dengue viruses: is it time to develop a universal vaccine?
Abstract Zika and the four serotypes of dengue are closely related flaviviruses that share a high degree of structural and sequence homology and co-circulate in many regions of the world. Here, we review recent studies investigating antigenic cross-reactivity between the two viruses. We discuss the pathogenic and protective roles of cross-reactive anti-viral antibody and T cell responses, respectively, in modulating the outcome of secondary dengue or Zika infection. Based on recent findings and increased incidence of severe disease in seronegative recipients of the first dengue vaccine to be licensed, we propose t...
Source: Current Opinion in Immunology - March 15, 2019 Category: Allergy & Immunology Authors: Wen J, Shresta S Tags: Curr Opin Immunol Source Type: research

Studying interactions between dendritic cells and T cells in vivo.
Abstract Antigen presentation is the key first step in the establishment of an antigen-specific T cell response. Among professional antigen presenting cells (APCs), dendritic cells (DCs) are the major population responsible for the priming of both CD4+ and CD8+ naïve T cells. This priming requires physical interaction between the DC and the T cell; during which signals are exchanged that determine both the magnitude and the quality of the ensuing response. The nature of these signals varies widely depending on the nature of the antigen, the anatomical site in which they take place, and the phenotype of the an...
Source: Current Opinion in Immunology - March 15, 2019 Category: Allergy & Immunology Authors: Chudnovskiy A, Pasqual G, Victora GD Tags: Curr Opin Immunol Source Type: research

Dendritic cells are what they eat: how their metabolism shapes T helper cell polarization.
Abstract Dendritic cells (DCs) are professional antigen-presenting cells that play a crucial role in the priming and differentiation of CD4+ T cells into several distinct subsets including effector T helper (Th) 1, Th17 and Th2 cells, as well as regulatory T cells (Tregs). It is becoming increasingly clear that cellular metabolism shapes the functional properties of DCs. Specifically, the ability of DCs to drive polarization of different Th cell subsets may be orchestrated by the engagement of distinct metabolic pathways. In this review, we will discuss the recent advances in the DC metabolism field, by focusing o...
Source: Current Opinion in Immunology - March 12, 2019 Category: Allergy & Immunology Authors: Patente TA, Pelgrom LR, Everts B Tags: Curr Opin Immunol Source Type: research

What B cell memories are made of.
Abstract In many ways, memory B cells represent the ultimate outcome of humoral immunity. Many of these cells express exceptionally high affinity antigen-specific B cell receptors for antigen, and these cells are a critical source of the long-lived plasma cells that secrete protective serum antibodies to protect against secondary exposure to pathogens and other life-threatening antigens. Evidence is now emerging that not all memory B cells are created via the same cellular pathways and molecular events. Similarly, it is becoming clear that different memory B cells can take on different functions, with some produci...
Source: Current Opinion in Immunology - March 9, 2019 Category: Allergy & Immunology Authors: Tomayko MM, Allman D Tags: Curr Opin Immunol Source Type: research

New technologies and applications in infant B cell immunology.
Abstract The human immune system changes dramatically with age, and early life exposures to pathogens and environmental antigens begin the formation of immune memory which influences subsequent responses later in life. To study infant immunity, sample-sparing experimental methods that extract maximal data from small samples of blood or other tissues are needed; fortunately, recent developments in high-throughput sequencing and multiplexed labeling and measurement of markers on cells are well-suited to these tasks. Here, we review some recent studies of infant immune responses to infectious disease, highlighting si...
Source: Current Opinion in Immunology - February 27, 2019 Category: Allergy & Immunology Authors: Nielsen SCA, Boyd SD Tags: Curr Opin Immunol Source Type: research

B cells in the formation of tertiary lymphoid organs in autoimmunity, transplantation and tumorigenesis.
Abstract Tertiary lymphoid organs named also tertiary lymphoid structures (TLS) often occur at sites of autoimmune inflammation, organ transplantation and cancer. Although the mechanisms for their formation/function are not entirely understood, it is known that TLS can display features of active germinal centres supporting the proliferation and differentiation of (auto)-reactive B cells. In this Review, we discuss current knowledge on TLS-associated B cells with particular reference on how within diseased tissues these structures are linked to either deleterious or protective outcomes in patients and the potential...
Source: Current Opinion in Immunology - February 21, 2019 Category: Allergy & Immunology Authors: Corsiero E, Delvecchio FR, Bombardieri M, Pitzalis C Tags: Curr Opin Immunol Source Type: research

T-bet+ B cells: A common denominator in protective and autoreactive antibody responses?
Abstract T-bet+ B cells have emerged as a key component of the humoral immune response in both infections and autoimmune disorders, with many of their phenotypic and functional attributes conserved between mice and humans. They are protective (infections) and pathogenic (autoimmunity), although the associated commonalities and differences remain unclear. Heterogeneity within this pool, in terms of origin, fate and function may underlie these divergent roles. Their significance is context-dependent- they may constitute a persistent effector memory cell pool, or products of recent primary responses. In both cases ho...
Source: Current Opinion in Immunology - February 19, 2019 Category: Allergy & Immunology Authors: Myles A, Sanz I, Cancro MP Tags: Curr Opin Immunol Source Type: research

MHC I chaperone complexes shaping immunity.
te; R Abstract Major histocompatibility complex class I (MHC I) molecules present peptides on the surface of most nucleated cells and allow the immune system to detect and eliminate infected or malignantly transformed cells. The peptides are derived from endogenous proteins by proteasomal degradation or aberrant translation, and are translocated from the cytosol into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP), a central component of the peptide-loading complex (PLC). The peptides are subsequently processed by ER-resident aminopeptidases (ERAP1/2) and loaded onto MHC ...
Source: Current Opinion in Immunology - February 13, 2019 Category: Allergy & Immunology Authors: Thomas C, Tampé R Tags: Curr Opin Immunol Source Type: research

The labyrinth unfolds: architectural rearrangements of the endolysosomal system in antigen-presenting cells.
Abstract Antigen-presenting cells (APCs) capture and present pathogens to T cells, thus arousing adaptive immune responses geared at the elimination of these invaders. In APCs, pathogens acquired from the extracellular space intersect with MHC class II (MHC-II) molecules in the endolysosomal system, where processing and loading of antigenic peptides occur. The resulting complexes can then be directed to the cell surface for recognition by T cells. To achieve this, the endosomal pathway of APCs must undergo dramatic rearrangements upon pathogen encounter. In this review we discuss recent strides in our understandin...
Source: Current Opinion in Immunology - February 6, 2019 Category: Allergy & Immunology Authors: Perrin P, Jongsma ML, Neefjes J, Berlin I Tags: Curr Opin Immunol Source Type: research

Affinity war: forging immunoglobulin repertoires.
Abstract B cell immunoglobulin (Ig) repertoire composition shapes immune responses. The generation of Ig diversity begins with Ig variable region exon assembly from gene segments, random inter-segment junction sequence diversity, and combinations of Ig heavy and light chain. This generates vast preemptive sequence freedom in early developing B lineage cell Ig genes that can anticipate a great diversity of threats. This freedom is met with large restrictions that ultimately define the naïve (i.e. preimmune) Ig repertoire. Activation-induced somatic hypermutation (SHM), which further diversifies Ig V regions, i...
Source: Current Opinion in Immunology - January 25, 2019 Category: Allergy & Immunology Authors: Zuo T, Gautam A, Wesemann DR Tags: Curr Opin Immunol Source Type: research

B-1 cell responses to infections.
Abstract B-1 cells represent an innate-like early-developing B cell population, whose existence as an independent lymphocyte subset has been questioned in the past. Recent molecular and lineage tracing studies have not only confirmed their unique origins and differentiation paths, they have also provided a rationale for their distinctive functionalities compared to conventional B cells. This review summarizes our current understanding of B-1 cell development, and the activation events that regulate B-1 cell responses to self and foreign antigens. We discuss the unresolved question to what extent BCR engagement, th...
Source: Current Opinion in Immunology - January 24, 2019 Category: Allergy & Immunology Authors: Smith FL, Baumgarth N Tags: Curr Opin Immunol Source Type: research

Microbiome control of innate reactivity.
Abstract Numerous scientific disciplines, including immunology, are now positioned to fully realize the potential of the intestinal microbiome to modulate a wide array of basic processes. Increasingly, microbiota-derived metabolites are being recognized for mediating these effects. Coupled with advances in large scale sequencing and mass spectrometry, research into the microbiota and their metabolites has entered into an era of rapid discovery. Here, we review recent studies that have shown how-specific metabolic products of the microbiome alter properties of the innate immune system that in turn modulate response...
Source: Current Opinion in Immunology - January 21, 2019 Category: Allergy & Immunology Authors: Chen F, Stappenbeck TS Tags: Curr Opin Immunol Source Type: research

Cellular pathways in the development of human and murine innate lymphoid cells.
Abstract Innate lymphoid cells (ILCs) are critical to effective immune surveillance against pathogens, have malignant counterparts, and contribute to disease. Thus, it is important to understand ILC development. All ILCs are derived from the common lymphoid progenitor cell; however, the exact mechanisms and signals that initiate their divergence from T cells, B cells and one and other are incompletely understood. Evidence now supports a stepwise developmental process that includes distinct cellular intermediates, progressively narrowed differentiation, and some plasticity. While the current models of human and mur...
Source: Current Opinion in Immunology - December 19, 2018 Category: Allergy & Immunology Authors: Scoville SD, Freud AG, Caligiuri MA Tags: Curr Opin Immunol Source Type: research

Neuronal regulation of innate lymphoid cells.
Abstract The cardinal signs of inflammation suggest a close connection between the nervous system and the immune system. However, the cellular and molecular basis of these interactions remains incompletely defined. Recent research has demonstrated that tissue-resident innate lymphoid cells (ILCs) obtain neuronal signals, particularly at mucosal barriers, where ILCs regulate tissue homeostasis. New developments in our understanding of neuronal regulation of ILCs provide insight into how immune responses in tissues are precisely targeted, spatially regulated, and how ILCs sense environmental changes and disturbance ...
Source: Current Opinion in Immunology - December 7, 2018 Category: Allergy & Immunology Authors: Klose CS, Artis D Tags: Curr Opin Immunol Source Type: research

Innate lymphoid cell sensing of tissue vitality.
Abstract Innate lymphoid cells (ILCs) constitute a heterogeneous population of cytokine-secreting cells that colonize different tissues and are heavily reliant on cytokines and other secreted factors for their development, maintenance and effector functions. Most ILCs are tissue resident and differentiate in non-lymphoid peripheral tissues. As tissue-resident sentinels, ILCs must rapidly identify pathogens or malignancy in an effort to return the tissue to homeostasis. Here we review the mechanisms that ILCs employ to sense cytokines and other potent immunoregulatory factors that promote their development in diffe...
Source: Current Opinion in Immunology - December 4, 2018 Category: Allergy & Immunology Authors: Barrow AD, Colonna M Tags: Curr Opin Immunol Source Type: research

ILC2s - resident lymphocytes pre-adapted to a specific tissue or migratory effectors that adapt to where they move?
Abstract A cardinal feature of the T-cell adaptive immune system is the antigen-dependent activation of naïve T cells in secondary lymphoid sites, followed by the migration of the resultant effector cells through the efferent lymph to the blood and then into a peripheral tissue site of infection or tumor growth. In contrast, the current view of innate lymphocytes (ILCs), the innate counterparts of T cells, is that they are tissue-resident cells, adapted to their specific environments during development and performing their effector functions locally upon cytokine stimulation. Here we present recent findings t...
Source: Current Opinion in Immunology - November 22, 2018 Category: Allergy & Immunology Authors: Germain RN, Huang Y Tags: Curr Opin Immunol Source Type: research