Cell-Free Therapies: Novel Approaches for COVID-19
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors —The Current Status
Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease - 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. The clinical manifestations of this disease are pneumonia, lung injury, inflammation, and severe acute respiratory syndrome (SARS). Currently, there is no vaccine or effective pharmacological agents available for the prevention/treatment of SARS-CoV2 infections. Moreover, deve...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Matrix Metalloproteinase-12 Is Required for Granuloma Progression
ConclusionsThe striking reduction of granuloma formation at day 60 in Mmp12 KO mice suggests that MMP12 is required to maintain chronic granuloma pathophysiology. The increased PPARγ and decreased IFNγ findings suggest that these mediators also may be involved since previous studies have shown that PPARγ suppresses IFNγ and PPARγ deficiency amplifies granuloma formation. Interestingly, a role of MMP12 in granuloma resolution is also suggested by increases in both macrophage influx and CCL2. Overall, our results strongly implicate MMP12 as a key factor in granuloma persistence and as a possible...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Human Chondrocyte Activation by Toxins From Premolis semirufa, an Amazon Rainforest Moth Caterpillar: Identifying an Osteoarthritis Signature
Pararamosis is a disease that occurs due to contact with the hairs of the larval stage of the Brazilian moth Premolis semirufa. Envenomation induces osteoarticular alterations with cartilage impairment that resembles joint synovitis. Thus, the toxic venom present in the caterpillar hairs interferes with the phenotype of the cells present in the joints, resulting in inflammation and promoting tissue injury. Therefore, to address the inflammatory mechanisms triggered by envenomation, we studied the effects of P. semirufa hair extract on human chondrocytes. We have selected for the investigation, cytokines, chemokines, matrix...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Gene Expression in Spontaneous Experimental Autoimmune Encephalomyelitis Is Linked to Human Multiple Sclerosis Risk Genes
Recent genome-wide association studies have identified over 230 genetic risk loci for multiple sclerosis. Current experimental autoimmune encephalomyelitis (EAE) models requiring active induction of disease may not be optimally suited for the characterization of the function of these genes. We have thus used gene expression profiling to study whether spontaneous opticospinal EAE (OSE) or MOG-induced EAE mirrors the genetic contribution to the pathogenesis of multiple sclerosis more faithfully. To this end, we compared gene expression in OSE and MOG EAE models and analyzed the relationship of both models to human multiple s...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

MicroRNAs of Human Herpesvirus 6A and 6B in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients
Human herpesvirus-6A (HHV-6A) and −6B (HHV-6B) might be involved in the etiopathogenesis of multiple sclerosis (MS), especially the HHV-6A. We aim at assessing, for the first time in the scientific literature, the HHV-6A/B microRNAs in MS patients. We analyzed the miRNAs of HHV-6A: miR-U86, and −6B: hhv6b-miR-Ro6-1, −2, −3-3p, −3-5p, and −4 in paired samples of serum and CSF of 42 untreated MS patients and 23 patients with other neurological diseases (OND), using Taqman MicroRNA Assays. Intrathecal HHV-6A/B antibody production and anti-HHV-6A/B IgG/IgM levels in serum were measured. MS c...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Transcriptome Profiling of Human Monocyte-Derived Macrophages Upon CCL2 Neutralization Reveals an Association Between Activation of Innate Immune Pathways and Restriction of HIV-1 Gene Expression
We report that exposure to CCL2 neutralizing antibody profoundly affected the MDM transcriptome. Functional annotation clustering of up-regulated genes identified two clusters enriched for antiviral defense and immune response pathways, comprising several interferon-stimulated, and restriction factor coding genes. Transcripts in the clusters were enriched for RELA and NFKB1 targets, suggesting the activation of the canonical nuclear factor κB pathway as part of a regulatory network involving miR-155 up-regulation. Furthermore, while HIV-1 infection caused small changes to the MDM transcriptome, with no evidence of ho...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

CNS Macrophages and Infant Infections
The central nervous system (CNS) harbors its own immune system composed of microglia in the parenchyma and CNS-associated macrophages (CAMs) in the perivascular space, leptomeninges, dura mater, and choroid plexus. Recent advances in understanding the CNS resident immune cells gave new insights into development, maturation and function of its immune guard. Microglia and CAMs undergo essential steps of differentiation and maturation triggered by environmental factors as well as intrinsic transcriptional programs throughout embryonic and postnatal development. These shaping steps allow the macrophages to adapt to their speci...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Macrophage TLR4 and PAR2 Signaling: Role in Regulating Vascular Inflammatory Injury and Repair
Macrophages play a central role in dictating the tissue response to infection and orchestrating subsequent repair of the damage. In this context, macrophages residing in the lungs continuously sense and discriminate among a wide range of insults to initiate the immune responses important to host-defense. Inflammatory tissue injury also leads to activation of proteases, and thereby the coagulation pathway, to optimize injury and repair post-infection. However, long-lasting inflammatory triggers from macrophages can impair the lung's ability to recover from severe injury, leading to increased lung vascular permeability and n...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Mumps Outbreaks in Vaccinated Populations —Is It Time to Re-assess the Clinical Efficacy of Vaccines?
History illustrates the remarkable public health impact of mass vaccination, by dramatically improving life expectancy and reducing the burden of infectious diseases and co-morbidities worldwide. It has been perceived that if an individual adhered to the MMR vaccine schedule that immunity to mumps virus (MuV) would be lifelong. Recent mumps outbreaks in individuals who had received two doses of the Measles Mumps Rubella (MMR) vaccine has challenged the efficacy of the MMR vaccine. However, clinical symptoms, complications, viral shedding and transmission associated with mumps infection has been shown to be reduced in vacci...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

The Evolving Landscape of PD-1/PD-L1 Pathway in Head and Neck Cancer
Over the past 10 years, cancer immunotherapy has made significant progress in multiple cancer types and has been gradually been applied to clinical cancer care, in which the programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is one of the most attractive targets. Compared with traditional therapies, the emerging PD-1/PD-L1 blockade immunotherapy exhibited more satisfactory curative effects and lower toxicity for patients with advanced head and neck squamous cell carcinoma (HNSCC). This review analyzes the expression characteristics and clinical significance of PD-1/PD-L1 in HNSCC, the imm...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Mast Cells in Alveolar Septa of COVID-19 Patients: A Pathogenic Pathway That May Link Interstitial Edema to Immunothrombosis
It is currently believed that innate immunity is unable to prevent the spread of SARS-CoV-2 from the upper airways to the alveoli of high-risk groups of patients. SARS-CoV-2 replication in ACE-2-expressing pneumocytes can drive the diffuse alveolar injury through the cytokine storm and immunothrombosis by upregulating the transcription of chemokine/cytokines, unlike several other respiratory viruses. Here we report histopathology data obtained in post-mortem lung biopsies of COVID-19, showing the increased density of perivascular and septal mast cells (MCs) and IL-4-expressing cells (n = 6), in contrast to the numbers foun...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

β-Arrestin1 and β-Arrestin2 Are Required to Support the Activity of the CXCL12/HMGB1 Heterocomplex on CXCR4
In conclusion, the CXCL12/HMGB1 heterocomplex engages the β-arrestin proteins differently from CXCL12, promoting a prompt availability of CXCR4 on the cell surface, and enhancing directional cell migration. These data unveil the signaling induced by the CXCL12/HMGB1 heterocomplex in view of identifying biased CXCR4 antagonists or agonists targeting the variety of functions it exerts. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Eosinophils Control Liver Damage by Modulating Immune Responses Against Fasciola hepatica
In conclusion, we demonstrate that eosinophils are beneficial for the host during F. hepatica infection, by limiting the production of IL-10 by specific CD4+ T cells and favoring eosinophil degranulation induced by specific antibodies. This work contributes to a better understanding of the role of eosinophils in parasitic helminth infections. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Hip Fracture Leads to Transitory Immune Imprint in Older Patients
Conclusion: HF is associated with several transitory immunological changes including pro-inflammatory phenotype in innate compartment and immunosuppressive profile in adaptive compartment. A comprehensive assessment of immune mechanisms implicated in the patient's prognosis after HF could pave the way to develop new immune therapeutics strategies. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Glucocorticoids Regulate Circadian Rhythm of Innate and Adaptive Immunity
Animals have evolved circadian rhythms to adapt to the 24-h day-night cycle. Circadian rhythms are controlled by molecular clocks in the brain and periphery, which is driven by clock genes. The circadian rhythm is propagated from the brain to the periphery by nerves and hormones. Glucocorticoids (GCs) are a class of steroid hormones produced by the adrenal cortex under the control of the circadian rhythm and the stress. GCs have both positive and negative effects on the immune system. Indeed, they are well known for their strong anti-inflammatory and immunosuppressive effects. Endogenous GCs inhibit the expression of infla...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Communications Between Peripheral and the Brain-Resident Immune System in Neuronal Regeneration After Stroke
Cerebral ischemia may cause irreversible neural network damage and result in functional deficits. Targeting neuronal repair after stroke potentiates the formation of new connections, which can be translated into a better functional outcome. Innate and adaptive immune responses in the brain and the periphery triggered by ischemic damage participate in regulating neural repair after a stroke. Immune cells in the blood circulation and gut lymphatic tissues that have been shaped by immune components including gut microbiota and metabolites can infiltrate the ischemic brain and, once there, influence neuronal regeneration eithe...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Chemokines in Non-alcoholic Fatty Liver Disease: A Systematic Review and Network Meta-Analysis
Conclusion: Elevated concentrations of CCL2, CCL4, CCL20, CXCL8, and CXCL10 may be associated with NAFL or NASH. In this regard, more population-based studies are needed to ascertain this hypothesis.Systematic Review Registration: PROSPERO: CRD42020139373. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

CD4+ T Cell Defects in a Mulibrey Patient With Specific TRIM37 Mutations
Mulibrey (muscle-liver-brain-eye) syndrome (MUL) is an autosomal recessive disorder caused by mutations in the TRIpartite motif (TRIM)37 gene, encoding for TRIM37 a member of the TRIM E3 ubiquitin ligase protein family. MUL patients are characterized by growth retardation, dysmorphic features, and a wide range of abnormalities affecting different organs. However, T-cell abnormalities have not been observed in MUL subjects, to date. Here we described the immunological features of a MUL child carrying recently identified TRIM37 mutations, a 17q22 deletion of maternal origin combined with a TRIM37 variant of paternal origin. ...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Colorectal Cancer Immunotherapy: Options and Strategies
Colorectal cancer is the third most common cancer in the world with increasing incidence and mortality rates globally. Standard treatments for colorectal cancer have always been surgery, chemotherapy and radiotherapy which may be used in combination to treat patients. However, these treatments have many side effects due to their non-specificity and cytotoxicity toward any cells including normal cells that are growing and dividing. Furthermore, many patients succumb to relapse even after a series of treatments. Thus, it is crucial to have more alternative and effective treatments to treat CRC patients. Immunotherapy is one ...
Source: Frontiers in Immunology - September 18, 2020 Category: Allergy & Immunology Source Type: research

Immunopathogenesis of COVID-19: Summary and Possible Interventions
Since the onset of the COVID-19 pandemic in the fall of 2019 over 4 million people have been infected and over 280,000 have died (1). Information about the SARS-CoV2 virus is evolving rapidly. At this time there are no interventions proven to be effective for cases infected with SARS-CoV2. Current knowledge about the clinical and laboratory manifestations of COVID-19 infection is reviewed and combined with knowledge about the immunopathogenic mechanisms of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV1) and Middle East Respiratory Syndrome (MERS) to formulate theories and suggest possible therapeutic intervention...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Platelets and Their Role in the Pathogenesis of Cardiovascular Events in Patients With Community-Acquired Pneumonia
Community-acquired pneumonia (CAP) remains an important cause of morbidity and mortality throughout the world with much recent and ongoing research focused on the occurrence of cardiovascular events (CVEs) during the infection, which are associated with adverse short-term and long-term survival. Much of the research directed at unraveling the pathogenesis of these events has been undertaken in the settings of experimental and clinical CAP caused by the dangerous, bacterial respiratory pathogen, Streptococcus pneumoniae (pneumococcus), which remains the most common bacterial cause of CAP. Studies of this type have revealed ...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Costimulation Blockade in Vascularized Composite Allotransplantation
Vascular composite allotransplantation (VCA) is a field under research and has emerged as an alternative option for the repair of severe disfiguring defects that result from infections or traumatic amputation in a selected group of patients. VCA is performed in centers with appropriate expertise, experience and adequate resources to effectively manage the complexity and complications of this treatment. Lifelong immunosuppressive therapy, immunosuppression associated complications, and the effects of the host immune response in the graft are major concerns in VCA. VCA is considered a quality of life transplant and the risk-...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Immunomodulation and Immune Escape Strategies of Gastrointestinal Helminths and Schistosomes
Parasitic worms (helminths) developed various immunoregulatory mechanisms to counteract the immune system of their host. The increasing identification and characterization of helminth-derived factors with strong immune modulatory activity provides novel insights into immune escape strategies of helminths. Such factors might be good targets to enhance anti-helminthic immune responses. In addition, immunosuppressive helminth-derived factors could be useful to develop new therapeutic strategies for treatment of chronic inflammatory conditions. This review will take an in depth look at the effects of immunomodulatory molecules...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Blocking of the High-Affinity Interaction-Synapse Between SARS-CoV-2 Spike and Human ACE2 Proteins Likely Requires Multiple High-Affinity Antibodies: An Immune Perspective
The pandemic of Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2 has induced global eagerness to develop vaccines and therapeutics for treating COVID-19, including neutralizing antibodies. To develop effective therapeutic antibodies against SARS-CoV-2, it is critical to understand the interaction between viral and host's proteins. The human ACE2 (hACE2) protein is the crucial target for the SARS-CoV's Spike protein that allows the virus to adhere to host epithelial cells. X-ray crystal structures and biophysical properties of protein-protein interactions reveal a large interaction surface with high binding-affinity...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Editorial: The Role of the Gut Microbiota in Health and Inflammatory Diseases
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Biomarkers and Diagnostic Testing for Renal Disease in Sjogren's Syndrome
Primary Sjogren's syndrome (pSS) is an autoimmune disorder in which lymphocytic infiltration leads to lacrimal and salivary glands dysfunction, which results in symptoms of dryness (xerophthalmia and xerostomia). Extraglandular features are common and may affect several organs. Renal involvement has long been known as one of the systemic complications of pSS. The most classical lesion observed in pSS is tubulointerstitial nephritis (TIN) and less frequently membranoproliferative glomerulonephritis (MPGN), which is related to cryoglobulinemia. In some cases, renal biopsy is necessary for the definitive diagnosis of kidney i...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Single-Center Overview of Pediatric Monogenic Autoinflammatory Diseases in the Past Decade: A Summary and Beyond
Conclusions: The present study summarized both clinical and genetic characteristics of 18 kinds of monogenic AIDs found in the largest pediatric AID center over the past decade, with fever, skin problems, and musculoskeletal system disorders being the most prevalent clinical features. Many of the mutations were newly discovered. This is by far the first and largest monogenic AID report in Chinese pediatric population and also a catalog of the phenotypic and genotypic features among these patients. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Live Imaging of Innate and Adaptive Immune Responses in the Liver
Immune response in the liver is determined by the spatial organization and cellular dynamics of hepatic immune cells. The liver vasculature accommodates abundant tissue-resident innate immune cells, such as Kupffer cells, natural killer cells, and natural killer T cells, to ensure efficient intravascular immunosurveillance. The fenestrated sinusoids also allow direct contact between circulating T cells and non-canonical antigen-presenting cells, such as hepatocytes, to instruct adaptive immune responses. Distinct cellular behaviors are exploited by liver immune cells to exert proper functions. Intravital imaging enables re...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Scaffolding LSD1 Inhibitors Impair NK Cell Metabolism and Cytotoxic Function Through Depletion of Glutathione
Cell therapies such as chimeric-antigen receptor (CAR) T-cells and NK cells are cutting-edge methods for treating cancer and other diseases. There is high interest in optimizing drug treatment regimens to best work together with emerging cell therapies, such as targeting epigenetic enzymes to stimulate recognition of tumor cells by immune cells. Herein, we uncover new mechanisms of the histone demethylase LSD1, and various inhibitors targeting unique domains of LSD1, in the function of NK cells grown for cell therapy. Catalytic inhibitors (tranylcypromine and the structural derivatives GSK LSD1 and RN-1) can irreversibly b...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Innate Inspiration: Antifungal Peptides and Other Immunotherapeutics From the Host Immune Response
The purpose of this review is to describe antifungal therapeutic candidates in preclinical and clinical development derived from, or directly influenced by, the immune system, with a specific focus on antimicrobial peptides (AMP). Although the focus of this review is AMP with direct antimicrobial effects on fungi, we will also discuss compounds with direct antifungal activity, including monoclonal antibodies (mAb), as well as immunomodulatory molecules that can enhance the immune response to fungal infection, including immunomodulatory AMP, vaccines, checkpoint inhibitors, interferon and colony stimulating factors as well ...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Immunobiotic Lactobacillus jensenii TL2937 Alleviates Dextran Sodium Sulfate-Induced Colitis by Differentially Modulating the Transcriptomic Response of Intestinal Epithelial Cells
Immunobiotics have emerged as a promising intervention to alleviate intestinal damage in inflammatory bowel disease (IBD). However, the beneficial properties of immunobiotics are strain dependent and, therefore, each strain has to be evaluated in order to demonstrate its potential application in IBD. Our previous in vitro and in vivo studies demonstrated that Lactobacillus jensenii TL2937 attenuates gut acute inflammatory response triggered by Toll-like receptor 4 activation. However, its effect on colitis has not been evaluated before. In this work, we studied whether the TL2937 strain was able to protect against the deve...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Whole Transcriptome Analysis Reveals Heterogeneity in B Cell Memory Populations in Patients With Juvenile Idiopathic Arthritis-Associated Uveitis
PurposePatients with juvenile idiopathic arthritis (JIA) are prone to developing chronic anterior uveitis (JIA-U+). Although several risk factors for JIA-U+ have been identified, the underlying etiology is poorly understood. Histopathological studies demonstrate B cell infiltrates in eye tissues of patients with JIA-U+.MethodsWe performed transcriptome profiling of peripheral blood CD19-positive B cells taken from 14 cases with JIA-U+, 13 JIA cases without uveitis (JIA-U−), and five healthy controls. Deconvolution-based estimation was used to determine the immune cell fractions for each sample.ResultsDeconvolution re...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Flow Cytometric Analyses of Lymphocyte Markers in Immune Oncology: A Comprehensive Guidance for Validation Practice According to Laws and Standards
Many anticancer therapies such as antibody-based therapies, cellular therapeutics (e.g., genetically modified cells, regulators of cytokine signaling, and signal transduction), and other biologically tailored interventions strongly influence the immune system and require tools for research, diagnosis, and monitoring. In flow cytometry, in vitro diagnostic (IVD) test kits that have been compiled and validated by the manufacturer are not available for all requirements. Laboratories are therefore usually dependent on modifying commercially available assays or, most often, developing them to meet clinical needs. However, both ...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

CXCL4 Links Inflammation and Fibrosis by Reprogramming Monocyte-Derived Dendritic Cells in vitro
Fibrosis is a condition shared by numerous inflammatory diseases. Our incomplete understanding of the molecular mechanisms underlying fibrosis has severely hampered effective drug development. CXCL4 is associated with the onset and extent of fibrosis development in multiple inflammatory and fibrotic diseases. Here, we used monocyte-derived cells as a model system to study the effects of CXCL4 exposure on dendritic cell development by integrating 65 longitudinal and paired whole genome transcriptional and methylation profiles. Using data-driven gene regulatory network analyses, we demonstrate that CXCL4 dramatically alters ...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

A Double Edged Sword Role of Interleukin-22 in Wound Healing and Tissue Regeneration
Wound healing and tissue regeneration is an intricate biological process that involves repair of cellular damage and maintenance of tissue integrity. Cascades involved in wound healing and tissue regeneration highly overlap with cancer causing pathways. Usually, subsequent tissue damage events include release of a number of cytokines to accomplish post-trauma restoration. IL-22 is one of the cytokines that are immediately produced to initiate immune response against several tissue impairments. IL-22 is a fundamental mediator in inflammation, mucous production, protective role against pathogens, wound healing, and tissue re...
Source: Frontiers in Immunology - September 17, 2020 Category: Allergy & Immunology Source Type: research

Management of PTLD After Hematopoietic Stem Cell Transplantation: Immunological Perspectives
Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening complications of iatrogenic immune impairment after allogeneic hematopoietic stem cell transplantation (HSCT). In the pediatric setting, the majority of PTLDs are related to the Epstein–Barr virus (EBV) infection, and present as B-cell lymphoproliferations. Although considered rare events, PTLDs have been increasingly observed with the widening application of HSCT from alternative sources, including cord blood and HLA-haploidentical stem cell grafts, and the use of novel agents for the prevention and treatment of rejection and graft-vs.-host d...
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

Thrombomodulin as a Physiological Modulator of Intravascular Injury
Thrombomodulin (TM), which is predominantly expressed on the endothelium, plays an important role in maintaining vascular homeostasis by regulating the coagulation system. Intravascular injury and inflammation are complicated physiological processes that are induced by injured endothelium-mediated pro-coagulant signaling, necrotic endothelial- and blood cell-derived damage-associated molecular patterns (DAMPs), and DAMP-mediated inflammation. During the hypercoagulable state after endothelial injury, TM is released into the intravascular space by proteolytic cleavage of the endothelium component. Recombinant TM (rTM) is cl...
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

Staphylococcus epidermidis Boosts Innate Immune Response by Activation of Gamma Delta T Cells and Induction of Perforin-2 in Human Skin
Perforin-2 (P-2) is an antimicrobial protein with unique properties to kill intracellular bacteria. Gamma delta (GD) T cells, as the major T cell population in epithelial tissues, play a central role in protective and pathogenic immune responses in the skin. However, the tissue-specific mechanisms that control the innate immune response and the effector functions of GD T cells, especially the cross-talk with commensal organisms, are not very well understood. We hypothesized that the most prevalent skin commensal microorganism, Staphylococcus epidermidis, may play a role in regulating GD T cell-mediated cutaneous responses....
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

Challenges for the Newborn Following Influenza Virus Infection and Prospects for an Effective Vaccine
Newborns are at significantly increased risk of severe disease following infection with influenza virus. This is the collective result of their naïve status, altered immune responsiveness, and the lack of a vaccine that is effective in these individuals. Numerous studies have revealed impairments in both the innate and adaptive arms of the immune system of newborns. The consequence of these alterations is a quantitative and qualitative decrease in both antibody and T cell responses. This review summarizes the hurdles newborns experience in mounting an effective response that can clear influenza virus and limit disease...
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

Bacteria That Cause Enteric Diseases Stimulate Distinct Humoral Immune Responses
This article suggests that such variance could be contributory to persistent and recurrent disease. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

Impact of Gallic Acid on Gut Health: Focus on the Gut Microbiome, Immune Response, and Mechanisms of Action
Gallic acid (GA) is a naturally occurring polyphenol compound present in fruits, vegetables, and herbal medicines. According to previous studies, GA has many biological properties, including antioxidant, anticancer, anti-inflammatory, and antimicrobial properties. GA and its derivatives have multiple industrial uses, such as food supplements or additives. Additionally, recent studies have shown that GA and its derivatives not only enhance gut microbiome (GM) activities, but also modulate immune responses. Thus, GA has great potential to facilitate natural defense against microbial infections and modulate the immune respons...
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

Editorial: Autoantibodies in Kidney Diseases
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

Gut Microbiota-Dependent Trimethylamine N-Oxide Associates With Inflammation in Common Variable Immunodeficiency
A substantial proportion of patients with common variable immunodeficiency (CVID) have inflammatory and autoimmune complications of unknown etiology. We have previously shown that systemic inflammation in CVID correlates with their gut microbial dysbiosis. The gut microbiota dependent metabolite trimethylamine N-oxide (TMAO) has been linked to several metabolic and inflammatory disorders, but has hitherto not been investigated in relation to CVID. We hypothesized that TMAO is involved in systemic inflammation in CVID. To explore this, we measured plasma concentrations of TMAO, inflammatory markers, and lipopolysaccharide (...
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

Postnatal Expansion, Maturation, and Functionality of MR1T Cells in Humans
MR1-restricted T (MR1T) cells are defined by their recognition of metabolite antigens presented by the monomorphic MHC class 1-related molecule, MR1, the most highly conserved MHC class I related molecule in mammalian species. Mucosal-associated invariant T (MAIT) cells are the predominant subset of MR1T cells expressing an invariant TCR α-chain, TRAV1-2. These cells comprise a T cell subset that recognizes and mediates host immune responses to a broad array of microbial pathogens, including Mycobacterium tuberculosis. Here, we sought to characterize development of circulating human MR1T cells as defined by MR1-5-OP-...
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

Impact of Helminth Infection on Metabolic and Immune Homeostasis in Non-diabetic Obesity
Several epidemiological and immunological studies indicate a reciprocal association between obesity/metabolic syndrome and helminth infections. Numerous studies demonstrated that obesity is concomitant with chronic low-grade inflammation, which is marked by vital changes in cellular composition and function of adipose tissue. However, the effect of helminth infection on the homeostatic milieu in obesity is not well-understood. To determine the relationship between Strongyloides stercoralis (Ss) infection and obesity, we examined an array of parameters linked with obesity both before and at 6 months following anthelmintic t...
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

Pro-tumor γδ T Cells in Human Cancer: Polarization, Mechanisms of Action, and Implications for Therapy
The tumor immune microenvironment contributes to tumor initiation, progression and response to therapy. Among the immune cell subsets that play a role in the tumor microenvironment, innate-like T cells that express T cell receptors composed of γ and δ chains (γδ T cells) are of particular interest. Indeed, γδ T cells contribute to the immune response against many cancers, notably through their powerful effector functions that lead to the elimination of tumor cells and the recruitment of other immune cells. However, their presence in the tumor microenvironment has been associated with poo...
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

Plant-Derived Trimeric CO-26K-Equivalent Epitope Induced Neutralizing Antibodies Against Porcine Epidemic Diarrhea Virus
Porcine epidemic diarrhea virus (PEDV) is a causative agent of a highly infectious disease with a high mortality rate, especially in newborn piglets in Asian countries resulting in serious economic loss. The development of a rapid, safe, effective and cost-efficient vaccine is crucial to protect pigs against PEDV infection. The COE antigen is regarded to be a major target for subunit vaccine development against PEDV infection. The naturally assembled COE protein forms a homotrimeric structure. In the present study, we successfully produced a trimeric COE protein as a native structure by fusion with the C-terminal isoleucin...
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

The TLR4-MyD88 Signaling Axis Regulates Lung Monocyte Differentiation Pathways in Response to Streptococcus pneumoniae
In this study, lung myeloid-cell populations responsible for the innate immune response (IIR) against S. pneumoniae, and their dependence on the TLR4-signaling axis, were analyzed in TLR4–/– and Myeloid-Differentiation factor-88 deficient (MyD88–/–) mice. Neutrophils and monocyte-derived cells were recruited in infected mice 3-days post-infection. Compared to wild-type mice, there was an increased bacterial load in both these deficient mouse strains and an altered IIR, although TLR4–/– mice were more susceptible to bacterial infection. These mice also developed fewer alveolar macrophages...
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research

Thymic Stromal Lymphopoietin and Cancer: Th2-Dependent and -Independent Mechanisms
The thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine originally cloned from a murine thymic stromal cell line, and subsequently a human homolog was identified using database search methods. Human TSLP is mostly expressed in epithelial cells, among which are keratinocytes as well as stromal cells such as fibroblasts and immune cells. Human TSLP was first described to activate myeloid dendritic cells, which prime naïve T helper cells to produce high concentrations of Th2 cytokines, thus representing a key cytokine in triggering dendritic cells-mediated allergic Th2 inflammation. TSLP and/or its receptor has ...
Source: Frontiers in Immunology - September 16, 2020 Category: Allergy & Immunology Source Type: research