Enhancing Situational Awareness to Prevent Infectious Disease Outbreaks from Becoming Catastrophic.
Authors: Lipsitch M, Santillana M Abstract Catastrophic epidemics, if they occur, will very likely start from localized and far smaller (non-catastrophic) outbreaks that grow into much greater threats. One key bulwark against this outcome is the ability of governments and the health sector more generally to make informed decisions about control measures based on accurate understanding of the current and future extent of the outbreak. Situation reporting is the activity of periodically summarizing the state of the outbreak in a (usually) public way. We delineate key classes of decisions whose quality depends on high...
Source: Current Topics in Microbiology and Immunology - July 14, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

The Role of Melanin in Fungal Pathogenesis for Animal Hosts.
Authors: Smith DFQ, Casadevall A Abstract Melanins are a class of pigments that are ubiquitous throughout biology. They play incredibly diverse and important roles ranging from radiation protection to immune defense, camouflage, and virulence. Fungi have evolved to use melanin to be able to persist in the environment and within organisms. Fungal melanins are often located within the cell well and are able to neutralize reactive oxygen species and other radicals, defend against UV radiation, bind and sequester non-specific peptides and compounds, and produce a physical barrier that defends the cell. For this reason,...
Source: Current Topics in Microbiology and Immunology - July 8, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Diversity and Evolution of Type III Secreted Effectors: A Case Study of Three Families.
Authors: Bastedo DP, Lo T, Laflamme B, Desveaux D, Guttman DS Abstract A broad range of Gram-negative bacteria employ a type III secretion system (T3SS) to deliver virulence proteins termed type III secreted effectors directly into the cytoplasm of eukaryotic host cells. While effectors can contribute to the colonization of eukaryotic hosts by bacterial symbionts and pathogens, they can also elicit host immune responses that restrict bacterial growth. These opposing selective pressures have shaped the evolution of effector families and may be responsible for their incredible diversity in biochemical function, mecha...
Source: Current Topics in Microbiology and Immunology - June 28, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Assembly and Post-assembly Turnover and Dynamics in the Type III Secretion System.
This article aims to give an overview on the assembly and post-assembly dynamics of the T3SS, with a focus on emerging general concepts and adaptations of the general assembly pathway. PMID: 31218503 [PubMed - as supplied by publisher] (Source: Current Topics in Microbiology and Immunology)
Source: Current Topics in Microbiology and Immunology - June 22, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Artemisinin-Resistant Malaria as a Global Catastrophic Biological Threat.
Authors: Ricotta E, Kwan J Abstract The global spread of artemisinin resistance brings with it the threat of incurable malaria. Already, this disease threatens over 219 million lives per year and causes 5-6% losses in GDP in endemic areas, even with current advances in prevention and treatment. This chapter discusses the currently tenuous position we are in globally, and the impact that could be seen if artemisinin treatment is lost, whether due to the unchecked spread of K13 mutations or poor global investment in treatment and prevention advances. Artemisinin is the backbone of current ACT treatment programs and s...
Source: Current Topics in Microbiology and Immunology - June 22, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Transcriptional and Post-transcriptional Regulatory Mechanisms Controlling Type III Secretion.
Authors: Volk M, Vollmer I, Heroven AK, Dersch P Abstract Type III secretion systems (T3SSs) are utilized by numerous Gram-negative bacteria to efficiently interact with host cells and manipulate their function. Appropriate expression of type III secretion genes is achieved through the integration of multiple control elements and regulatory pathways that ultimately coordinate the activity of a central transcriptional activator usually belonging to the AraC/XylS family. Although several regulatory elements are conserved between different species and families, each pathogen uses a unique set of control factors and me...
Source: Current Topics in Microbiology and Immunology - June 22, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Export Mechanisms and Energy Transduction in Type-III Secretion Machines.
Authors: Renault TT, Guse A, Erhardt M Abstract The remarkably complex architecture and organization of bacterial nanomachines originally raised the enigma to how they are assembled in a coordinated manner. Over the years, the assembly processes of the flagellum and evolutionary-related injectisome complexes have been deciphered and were shown to rely on a conserved protein secretion machine: the type-III secretion system. In this book chapter, we demonstrate how individually evolved mechanisms cooperate in highly versatile and robust secretion machinery to export and assemble the building blocks of those nanomachi...
Source: Current Topics in Microbiology and Immunology - June 22, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

The Tip Complex: From Host Cell Sensing to Translocon Formation.
Authors: Picking WD, Barta ML Abstract Type III secretion systems are used by some Gram-negative bacteria to inject effector proteins into targeted eukaryotic cells for the benefit of the bacterium. The type III secretion injectisome is a complex nanomachine comprised of four main substructures including a cytoplasmic sorting platform, an envelope-spanning basal body, an extracellular needle and an exposed needle tip complex. Upon contact with a host cell, secretion is induced, resulting in the formation of a translocon pore in the host membrane. Translocon formation completes the conduit needed for effector secret...
Source: Current Topics in Microbiology and Immunology - June 22, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Flagellar Hook/Needle Length Control and Secretion Control in Type III Secretion Systems.
Authors: Aizawa SI Abstract The flagellum is a motile organ, and the needle complex is a type III secretion apparatus for pathogenesis. There are more similarities than differences between the two structures at the molecular level. Here I focus on the hook and the needle and discuss their length control mechanism. The hook is a substructure of the flagellum and the needle is a part of the needle complex. Both structures are tubular structures that have a central channel for protein secretion. Their lengths are controlled by an intriguing mechanism involving a ruler protein and a switchable gate of the protein secre...
Source: Current Topics in Microbiology and Immunology - June 12, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

The Type III Secretion System Sorting Platform.
Authors: Lara-Tejero M Abstract A central feature of type III protein secretion machines is their ability to engage their substrates in a hierarchical and organized fashion. The hierarchy in the secretion process is first observed during the assembly of the type III secretion injectisome when the secretion machine exclusively engages proteins required for building the needle complex substructure (early substrates). After completion of the needle complex, the secretion system loads the proteins that will form the needle tip substructure as well as the protein translocases (middle substrates), which upon contact with...
Source: Current Topics in Microbiology and Immunology - June 12, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Molecular Organization and Assembly of the Export Apparatus of Flagellar Type III Secretion Systems.
Authors: Minamino T, Kawamoto A, Kinoshita M, Namba K Abstract The bacterial flagellum is a supramolecular motility machine consisting of the basal body, the hook, and the filament. For construction of the flagellum beyond the cellular membranes, a type III protein export apparatus uses ATP and proton-motive force (PMF) across the cytoplasmic membrane as the energy sources to transport flagellar component proteins from the cytoplasm to the distal end of the growing flagellar structure. The protein export apparatus consists of a PMF-driven transmembrane export gate complex and a cytoplasmic ATPase complex. In additi...
Source: Current Topics in Microbiology and Immunology - June 8, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Inflammation, Immunity, and Vaccine Development for the Gastric Pathogen Helicobacter pylori.
This study provided new insight into the strategies for developing an improved vaccine for widespread use in countries with high infection rates and where gastric cancer (GC) remains one of the most common causes of death due to cancer. PMID: 31123883 [PubMed - in process] (Source: Current Topics in Microbiology and Immunology)
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Impact of Helicobacter pylori Virulence Factors on the Host Immune Response and Gastric Pathology.
Authors: Javed S, Skoog EC, Solnick JV Abstract Helicobacter pylori chronically infects nearly half the world's population, yet most of those infected remain asymptomatic throughout their lifetime. The outcome of infection-peptic ulcer disease or gastric cancer versus asymptomatic colonization-is a product of host genetics, environmental influences, and differences in bacterial virulence factors. Here, we review the current understanding of the cag pathogenicity island (cagPAI), the vacuolating cytotoxin (VacA), and a large family of outer membrane proteins (OMPs), which are among the best understood H. pylori viru...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Genetic Polymorphisms in Inflammatory and Other Regulators in Gastric Cancer: Risks and Clinical Consequences.
Authors: Rudnicka K, Backert S, Chmiela M Abstract Helicobacter pylori infection is associated with the development of a chronic inflammatory response, which may induce peptic ulcers, gastric cancer (GC), and mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic H. pylori infection promotes the genetic instability of gastric epithelial cells and interferes with the DNA repair systems in host cells. Colonization of the stomach with H. pylori is an important cause of non-cardia GC and gastric MALT lymphoma. The reduction of GC development in patients who underwent anti-H. pylori eradication schemes has also been...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

MALT Lymphoma as a Model of Chronic Inflammation-Induced Gastric Tumor Development.
Authors: Marcelis L, Tousseyn T, Sagaert X Abstract Mucosa-associated lymphoid tissue (MALT) lymphoma, or extranodal marginal zone lymphoma of MALT, is an indolent B-cell non-Hodgkin lymphoma linked with preexisting chronic inflammation. The stomach is the most commonly affected organ and the MALT lymphoma pathogenesis is clearly associated with Helicobacter pylori gastroduodenitis. Inflammation induces the lymphoid infiltrates in extranodal sites, where the lymphoma then subsequently develops. Genetic aberrations arise through the release of reactive oxygen species (ROS), H. pylori-induced endonucleases, and other...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Crosstalk Between DNA Damage and Inflammation in the Multiple Steps of Gastric Carcinogenesis.
Authors: Sokolova O, Naumann M Abstract Over the last years, intensive investigations in molecular biology and cell physiology extended tremendously the knowledge about the association of inflammation and cancer. In frame of this paradigm, the human pathogen Helicobacter pylori triggers gastritis and gastric ulcer disease, and contributes to the development of gastric cancer. Mechanisms, by which the bacteria-induced inflammation in gastric mucosa leads to intestinal metaplasia and carcinoma, are represented in this review. An altered cell-signaling response and increased production of free radicals by epithelial a...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Importance of Toll-like Receptors in Pro-inflammatory and Anti-inflammatory Responses by Helicobacter pylori Infection.
Authors: Nagashima H, Yamaoka Y Abstract Infectious diseases have been paramount among the threats to human health and survival throughout evolutionary history. Bacterial cell-surface molecules are key factors in the microorganism-host crosstalk, as they can interact with host pattern-recognition receptors (PRRs) of the gastrointestinal mucosa. The best-studied PRRs are toll-like receptors (TLRs). Because TLRs play an important key role in host defense, they have received increasing interest in the evolutionary and population genetics literature, and their variation represents a potential target of adaptive evoluti...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Role of NOD1 and ALPK1/TIFA Signalling in Innate Immunity Against Helicobacter pylori Infection.
Authors: Ying L, Ferrero RL Abstract The human pathogen Helicobacter pylori interacts intimately with gastric epithelial cells to induce inflammatory responses that are a hallmark of the infection. This inflammation is a critical precursor to the development of peptic ulcer disease and gastric cancer. A major driver of this inflammation is a type IV secretion system (T4SS) encoded by the cag pathogenicity island (cagPAI), present in a subpopulation of more virulent H. pylori strains. The cagPAI T4SS specifically activates signalling pathways in gastric epithelial cells that converge on the transcription factor, nuc...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Carbohydrate-Dependent and Antimicrobial Peptide Defence Mechanisms Against Helicobacter pylori Infections.
Authors: Padra M, Benktander J, Robinson K, Lindén SK Abstract The human stomach is a harsh and fluctuating environment for bacteria with hazards such as gastric acid and flow through of gastric contents into the intestine. H. pylori gains admission to a stable niche with nutrient access from exudates when attached to the epithelial cells under the mucus layer, whereof adherence to glycolipids and other factors provides stable and intimate attachment. To reach this niche, H. pylori must overcome mucosal defence mechanisms including the continuously secreted mucus layer, which provides several layers of defen...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

The Sweeping Role of Cholesterol Depletion in the Persistence of Helicobacter pylori Infections.
Authors: Morey P, Meyer TF Abstract The ability of Helicobacter pylori to persist lifelong in the human gastric mucosa is a striking phenomenon. It is even more surprising since infection is typically associated with a vivid inflammatory response. Recent studies revealed the mechanism by which this pathogen inhibits the epithelial responses to IFN-γ and other central inflammatory cytokines in order to abolish an effective antimicrobial defense. The mechanism is based on the modification and depletion of cholesterol by the pathogen's cholesterol-α-glucosyltransferase. It abrogates the assembly of numerou...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Helicobacter pylori Deregulates T and B Cell Signaling to Trigger Immune Evasion.
Authors: Reyes VE, Peniche AG Abstract Helicobacter pylori is a prevalent human pathogen that successfully establishes chronic infection, which leads to clinically significant gastric diseases including chronic gastritis, peptic ulcer disease (PUD), and gastric cancer (GC). H. pylori is able to produce a persistent infection due in large part to its ability to hijack the host immune response. The host adaptive immune response is activated to strategically and specifically attack pathogens and normally clears them from the infected host. Since B and T lymphocytes are central mediators of adaptive immunity, in this c...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Mechanisms of Inflammasome Signaling, microRNA Induction and Resolution of Inflammation by Helicobacter pylori.
Authors: Pachathundikandi SK, Blaser N, Backert S Abstract Inflammasome-controlled transcription and subsequent cleavage-mediated activation of mature IL-1β and IL-18 cytokines exemplify a crucial innate immune mechanism to combat intruding pathogens. Helicobacter pylori represents a predominant persistent infection in humans, affecting approximately half of the population worldwide, and is associated with the development of chronic gastritis, peptic ulcer disease, and gastric cancer. Studies in knockout mice have demonstrated that the pro-inflammatory cytokine IL-1β plays a central role in gastric tumori...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Impact of the Gastrointestinal Microbiome in Health and Disease: Co-evolution with the Host Immune System.
Authors: Hold GL, Hansen R Abstract Microbes within the gastrointestinal tract communicate with each other and with the host, which has profound effects on health and disease development. Only now, it is becoming apparent that how and when we acquire our own unique collection of "gut microbes" and also how we choose to maintain them is fundamental to our health. Helicobacter pylori is the most common bacterial infection worldwide, colonizing around half of the world's population, and is the major risk factor for gastric adenocarcinoma. More recently, it has also been shown to have some beneficial effects ...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Resolution of Gastric Cancer-Promoting Inflammation: A Novel Strategy for Anti-cancer Therapy.
Authors: Piazuelo MB, Riechelmann RP, Wilson KT, Algood HMS Abstract The connection between inflammation and cancer was initially recognized by Rudolf Virchow in the nineteenth century. During the last decades, a large body of evidence has provided support to his hypothesis, and now inflammation is recognized as one of the hallmarks of cancer, both in etiopathogenesis and ongoing tumor growth. Infection with the pathogen Helicobacter pylori is the primary causal factor in 90% of gastric cancer (GC) cases. As we increase our understanding of how chronic inflammation develops in the stomach and contributes to carcino...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Risk and Response to Biological Catastrophe in Lower Income Countries.
Authors: Luby S, Arthur R Abstract Natural and intentional biological risks threaten human civilization, both through direct human fatality as well as follow-on effects from a collapse of the just-in-time delivery system that provides food, energy and critical supplies to communities globally. Human beings have multiple innate cognitive biases that systematically impair careful consideration of these risks. Residents of low-income countries, especially those who live in rural areas and are less dependent upon global trade, may be the most resilient communities to catastrophic risks, but low-income countries also pr...
Source: Current Topics in Microbiology and Immunology - May 29, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Global Catastrophic Threats from the Fungal Kingdom : Fungal Catastrophic Threats.
Authors: Casadevall A Abstract The fungal kingdom poses major catastrophic threats to humanity but these are often unappreciated and minimized, in biological threat assessments. The causes for this blind spot are complex and include the remarkable natural resistance of humans to pathogenic fungi, the lack of contagiousness of human fungal diseases, and the indirectness of fungal threats, which are more likely to mediate their destructive effects on crops and ecosystems. A review of historical events reveals that the fungal kingdom includes major threats to humanity through their effects on human health, agriculture...
Source: Current Topics in Microbiology and Immunology - May 25, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

B Cells Carrying Antigen Receptors Against Microbes as Tools for Vaccine Discovery and Design.
Authors: Bhullar D, Nemazee D Abstract Can basic science improve the art of vaccinology? Here, we review efforts to understand immune responses with the aim to improve vaccine design and, eventually, to predict the efficacy of human vaccine candidates using the tools of transformed B cells and targeted transgenic mice carrying B cells with antigen receptors specific for microbes of interest. PMID: 30919086 [PubMed - as supplied by publisher] (Source: Current Topics in Microbiology and Immunology)
Source: Current Topics in Microbiology and Immunology - March 30, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Immunogenicity and Immunodominance in Antibody Responses.
Authors: Vogel M, Bachmann MF Abstract A large number of vaccines exist that control many of the most important infectious diseases. Despite these successes, there remain many pathogens without effective prophylactic vaccines. Notwithstanding strong difference in the biology of these infectious agents, there exist common problems in vaccine design. Many infectious agents have highly variable surface antigens and/or unusually high antibody levels are required for protection. Such high variability may be addressed by using conserved epitopes and these are, however, usually difficult to display with the right conforma...
Source: Current Topics in Microbiology and Immunology - March 30, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Understanding Molecular Pathogenesis with Chikungunya Virus Research Tools.
Authors: Carissimo G, Ng LFP Abstract Since its re-emergence in 2006, Chikungunya has been a major health concern in endemic areas. Transmitted by Aedes mosquitoes to mammalian hosts, Chikungunya leads to persistent debilitating symptoms in a high proportion of symptomatic human cases. In this review, we present several tools on the mosquito vector side as well as on the mammalian side that have been used to advance research on Chikungunya transmission and immunopathogenesis. These tools lead to key understandings of viral replication in both hosts, and innate and adaptive responses mediating virus clearance and pa...
Source: Current Topics in Microbiology and Immunology - March 20, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Cancer Explant Models.
Authors: Stackhouse CT, Gillespie GY, Willey CD Abstract Overcoming the challenges of understanding and treating cancer requires reliable patient-derived models of cancer (PDMCs). For decades, cancer research and therapeutic development relied primarily on cancer cell lines because of their prevalence, reproducibility, and simplicity to maintain. However, findings from research conducted in cell lines are rarely recapitulated in vivo and seldom directly translatable to patients. The tumor microenvironment (TME), tumor-stromal interactions, and associations with host immune cells produce profound changes in tumor ph...
Source: Current Topics in Microbiology and Immunology - March 20, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Preclinical Organotypic Models for the Assessment of Novel Cancer Therapeutics and Treatment.
Authors: Ward C, Meehan J, Gray M, Kunkler IH, Langdon SP, Murray A, Argyle D Abstract The immense costs in both financial terms and preclinical research effort that occur in the development of anticancer drugs are unfortunately not matched by a substantial increase in improved clinical therapies due to the high rate of failure during clinical trials. This may be due to issues with toxicity or lack of clinical effectiveness when the drug is evaluated in patients. Currently, much cancer research is driven by the need to develop therapies that can exploit cancer cell adaptations to conditions in the tumor microenviro...
Source: Current Topics in Microbiology and Immunology - March 14, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

IgE Glycosylation in Health and Disease.
Authors: Shade KT, Conroy ME, Anthony RM Abstract IgE are absolutely required for initiation of allergy reactions, which affect over 20% of the world's population. IgE are the least prevalent immunoglobulins in circulation with 12-h and 2-day half-lives in mouse and human serum, respectively, but an extended tissue half-life of 3-weeks bound to the surface of mast cells by the high affinity IgE receptor, FcεRI (Gould and Sutton 2008). Although the importance of glycosylation to IgG biology is well established, less is known regarding the contribution of IgE glycosylation to allergic inflammation. IgE has se...
Source: Current Topics in Microbiology and Immunology - March 4, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

IgG Fc Glycosylation in Human Immunity.
Authors: Wang TT Abstract Glycosylation of IgG Fc domains is a central mechanism in the diversification of antibody function. Modifications to the core Fc glycan impact antibody function by shifting the balance of Type I and Type II Fc gamma receptors (FcγR) that will be engaged by immune complexes. This, in turn, modulates the effector cells and functions that can be recruited during immune activation. Critically, humans have evolved to regulate Fc glycan modifications for immune homeostasis. Dysregulation in Fc glycan modifications can lead to loss of immune tolerance, symptomatic autoimmunity, and suscepti...
Source: Current Topics in Microbiology and Immunology - February 27, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Pancreatic Cancer Organotypic Models.
Authors: Coetzee A, Grose R, Kocher H Abstract Pancreatic cancer has a dismal prognosis for patients due to late diagnosis and ineffective treatment options. There is a desperate need for more accurate disease models to enable improved therapies and diagnostic tests to reach the clinic. Pancreatic tumours have a high content of desmoplastic stroma, which forms a stiff, hypoxic tumour mass and contributes significantly to tumour development and metastatic spread. Therefore, 2D cell culture is not sufficient for understanding the complex biology of this disease. 3D in vitro models offer a more representative method o...
Source: Current Topics in Microbiology and Immunology - February 24, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Fc Receptors in Antimicrobial Protection.
Authors: Wieland A, Ahmed R Abstract Antibodies are the key effector molecules of the humoral immune system providing long-term protective immunity against a wide range of pathogens and regulating immune responses. Traditionally, antibody-mediated protection against microbes was thought to be mainly a result of neutralizing Fab-antigen interaction; however, an increasing number of studies show the importance of proper FcR engagement for the protective capacity of antimicrobial antibodies. In this chapter, we review FcR-mediated effector functions contributing to antimicrobial protection in a direct and indirect man...
Source: Current Topics in Microbiology and Immunology - February 24, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Anti-inflammatory Activity of IgG-Fc.
Authors: Beneduce C, Kurtagic E, Bosques CJ Abstract Over 80 different autoimmune disorders have been identified. A common denominator across most of these disorders is the presence of pathogenic autoantibodies. The pathogenic and inflammatory nature of antibodies is well accepted, and over the last three decades, evidence in humans and rodent models has revealed that antibodies can induce anti-inflammatory activities. The discovery of the relationship between immunoglobulin G (IgG) glycovariants and disease activity in autoimmune patients has provided insight into the structural and functional characteristics of I...
Source: Current Topics in Microbiology and Immunology - February 24, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Immune Complex Vaccination.
Authors: Wen YM, Shi Y Abstract Antibody/antigen binding results in immune complexes (IC) that have a variety of regulatory functions. One important feature is the enhanced host immune activation against antigen contained in the complex. ICs play important roles at several critical steps that lead to B and T cell activation, including antigen targeting/retention, facilitated antigen uptake, antigen presenting cell activation and proper balancing of positive and negative stimulatory signals. In both poultry industry and clinical health care, ICs have been used as preventive and therapeutic vaccines. With our deepeni...
Source: Current Topics in Microbiology and Immunology - February 24, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Role of Fc ╬│Rs in Antibody-Based Cancer Therapy.
Role of FcγRs in Antibody-Based Cancer Therapy. Curr Top Microbiol Immunol. 2019 Feb 22;: Authors: Graziano RF, Engelhardt JJ Abstract Monoclonal antibodies can mediate antitumor activity by multiple mechanisms. They can bind directly to tumor receptors resulting in tumor cell death, or can bind to soluble growth factors, angiogenic factors, or their cognate receptors blocking signals required for tumor cell growth or survival. Monoclonal antibodies, upon binding to tumor cell, can also engage the host's immune system to mediate immune-mediated destruction of the tumor. The Fc portion of the anti...
Source: Current Topics in Microbiology and Immunology - February 24, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

IgG Fc Receptors: Evolutionary Considerations.
Authors: Bournazos S Abstract Immunoglobulins (Ig), a critical component of the adaptive immune system, are present in all jawed vertebrates and through sophisticated diversification mechanisms are able to recognize antigens of almost infinite diversity. During mammalian evolution, IgG has emerged as the predominant Ig isotype that is elicited upon antigenic challenge, representing the most abundant isotype present in circulation. Along with the IgG molecule, a family of specialized receptors has evolved in mammalian species that specifically recognize the Fc domain of IgG. These receptors, termed Fcγ recepto...
Source: Current Topics in Microbiology and Immunology - February 11, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Chronic Chikungunya Virus Disease.
Authors: McCarthy MK, Davenport BJJ, Morrison TE Abstract Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that has caused both small- and large-scale epidemics of incapacitating musculoskeletal disease across the globe. A substantial proportion of infected individuals experience debilitating arthralgia and/or arthritis that can persist in relapsing or continuous forms for months to years, an occurrence that appears independent of viral strain and outbreak location. Due to the lack of CHIKV-specific vaccine or therapeutics, treatment of chronic CHIKV disease is limited to supportive care. Although the...
Source: Current Topics in Microbiology and Immunology - January 19, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Molecular Virology of Chikungunya Virus.
Authors: Frolov I, Frolova EI Abstract Chikungunya virus (CHIKV) was discovered more than six decades ago, but has remained poorly investigated. However, after a recent outbreak of CHIK fever in both hemispheres and viral adaptation to new species of mosquitoes, it has attracted a lot of attention. The currently available experimental data suggest that molecular mechanisms of CHIKV replication in vertebrate and mosquito cells are similar to those of other New and Old World alphaviruses. However, this virus exhibits a number of unique characteristics that distinguish it from the other, better studied members of the ...
Source: Current Topics in Microbiology and Immunology - January 2, 2019 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Activity-Based Protein Profiling-Enabling Multimodal Functional Studies of Microbial Communities.
Authors: Whidbey C, Wright AT Abstract Microorganisms living in community are critical to life on Earth, playing numerous and profound roles in the environment and human and animal health. Though their essentiality to life is clear, the mechanistic underpinnings of community structure, interactions, and functions are largely unexplored and in need of function-dependent technologies to unravel the mysteries. Activity-based protein profiling offers unprecedented molecular-level characterization of functions within microbial communities and provides an avenue to determine how external exposures result in functional al...
Source: Current Topics in Microbiology and Immunology - November 9, 2018 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Cryptococcal Titan Cells: When Yeast Cells Are All Grown up.
Authors: García-Rodas R, de Oliveira HC, Trevijano-Contador N, Zaragoza O Abstract Cryptococcus neoformans is a human pathogenic yeast that causes hundreds of thousands of deaths worldwide among susceptible individuals, in particular, HIV+ patients. This yeast has developed several adaptation mechanisms that allow replication within the host. During decades, this yeast has been well known for a very peculiar and unique structure that contributes to virulence, a complex polysaccharide capsule that surrounds the cell wall. In contrast to other fungal pathogens, such as Candida albicans or Aspergillus fumigatus...
Source: Current Topics in Microbiology and Immunology - November 9, 2018 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

From Genes to Networks: The Regulatory Circuitry Controlling Candida albicans Morphogenesis.
Authors: Basso V, d'Enfert C, Znaidi S, Bachellier-Bassi S Abstract Candida albicans is a commensal yeast of most healthy individuals, but also one of the most prevalent human fungal pathogens. During adaptation to the mammalian host, C. albicans encounters different niches where it is exposed to several types of stress, including oxidative, nitrosative (e.g., immune system), osmotic (e.g., kidney and oral cavity) stresses and pH variation (e.g., gastrointestinal (GI) tract and vagina). C. albicans has developed the capacity to respond to the environmental changes by modifying its morphology, which comprises the ye...
Source: Current Topics in Microbiology and Immunology - October 30, 2018 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Overview and Comparison of Intestinal Organotypic Models, Intestinal Cells, and Intestinal Explants Used for Toxicity Studies.
Authors: Maresca M, Pinton P, Ajandouz EH, Menard S, Ferrier L, Oswald IP Abstract The intestine is a complex organ formed of different types of cell distributed in different layers of tissue. To minimize animal experiments, for decades, researchers have been trying to develop in vitro/ex vivo systems able to mimic the cellular diversity naturally found in the gut. Such models not only help our understanding of the gut physiology but also of intestinal toxicity. This review describes the different systems used to evaluate the effects of drugs/contaminants on intestinal functions and compares their advantages and li...
Source: Current Topics in Microbiology and Immunology - September 29, 2018 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

The Clock Keeps on Ticking: Emerging Roles for Circadian Regulation in the Control of Fungal Physiology and Pathogenesis.
Authors: Larrondo LF, Canessa P Abstract Tic-tac, tic-tac, the sound of time is familiar to us, yet, it also silently shapes daily biological processes conferring 24-hour rhythms in, among others, cellular and systemic signaling, gene expression, and metabolism. Indeed, circadian clocks are molecular machines that permit temporal control of a variety of processes in individuals, with a close to 24-hour period, optimizing cellular dynamics in synchrony with daily environmental cycles. For over three decades, the molecular bases of these clocks have been extensively described in the filamentous fungus Neurospora cras...
Source: Current Topics in Microbiology and Immunology - September 27, 2018 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

ABPP and Host-Virus Interactions.
Authors: Desrochers GF, Pezacki JP Abstract Successful viral infection, as well as any resultant antiviral response, relies on numerous sequential interactions between host and viral factors. These interactions can take the form of affinity-based interactions between viral and host macromolecules or active, enzyme-based interactions, consisting both of direct enzyme activity performed by viral enzymes and indirect modulation of the activity of the host cell's enzymes via viral interference. This activity has the potential to transform the local microenvironment to the benefit or detriment of both the virus and the ...
Source: Current Topics in Microbiology and Immunology - September 25, 2018 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Recent Advances in Activity-Based Protein Profiling of Proteases.
Authors: Chakrabarty S, Kahler JP, van de Plassche MAT, Vanhoutte R, Verhelst SHL Abstract The activity of proteases is tightly regulated, and dysregulation is linked to a variety of human diseases. For this reason, ABPP is a well-suited method to study protease biology and the design of protease probes has pushed the boundaries of ABPP. The development of highly selective protease probes is still a challenging task. After an introduction, the first section of this chapter discusses several strategies to enable detection of a single active protease species. These range from the usage of non-natural amino acids, com...
Source: Current Topics in Microbiology and Immunology - September 25, 2018 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Small-Molecule Inhibitors of PARPs: From Tools for Investigating ADP-Ribosylation to Therapeutics.
Authors: Kirby IT, Cohen MS Abstract Over the last 60 years, poly-ADP-ribose polymerases (PARPs, 17 family members in humans) have emerged as important regulators of physiology and disease. Small-molecule inhibitors have been essential tools for unraveling PARP function, and recently the first PARP inhibitors have been approved for the treatment of various human cancers. However, inhibitors have only been developed for a few PARPs and in vitro profiling has revealed that many of these exhibit polypharmacology across the PARP family. In this review, we discuss the history, development, and current state of the ...
Source: Current Topics in Microbiology and Immunology - September 23, 2018 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research

Extracellular Vesicles in Fungi: Composition and Functions.
Authors: de Toledo Martins S, Szwarc P, Goldenberg S, Alves LR Abstract The comprehension of fungal biology is important for several reasons. Besides being used in biotechnological processes and in the food industry, fungi are also important animal and vegetal pathogens. Fungal diseases in humans have a great importance worldwide, and understanding fungal biology is crucial for treatment and prevention of these diseases, especially because of emerging antifungal resistance that poses great epidemiological risks. Communication through extracellular vesicles is a ubiquitous mechanism of molecule transfer between cell...
Source: Current Topics in Microbiology and Immunology - September 23, 2018 Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research