scholarly journals Glycans in Virus-Host Interactions: A Structural Perspective

2021 ◽  
Vol 8 ◽  
Author(s):  
Nathaniel L. Miller ◽  
Thomas Clark ◽  
Rahul Raman ◽  
Ram Sasisekharan
Keyword(s):  
Immune System ◽  
Host Cells ◽  
Host Immune System ◽  
Host Interactions ◽  
Viral Glycoproteins ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Anti Hiv ◽  
Structural Perspective

Many interactions between microbes and their hosts are driven or influenced by glycans, whose heterogeneous and difficult to characterize structures have led to an underappreciation of their role in these interactions compared to protein-based interactions. Glycans decorate microbe glycoproteins to enhance attachment and fusion to host cells, provide stability, and evade the host immune system. Yet, the host immune system may also target these glycans as glycoepitopes. In this review, we provide a structural perspective on the role of glycans in host-microbe interactions, focusing primarily on viral glycoproteins and their interactions with host adaptive immunity. In particular, we discuss a class of topological glycoepitopes and their interactions with topological mAbs, using the anti-HIV mAb 2G12 as the archetypical example. We further offer our view that structure-based glycan targeting strategies are ready for application to viruses beyond HIV, and present our perspective on future development in this area.

scholarly journals Mucosal microbial parasites/symbionts in health and disease: an integrative overview

Parasitology ◽  
2019 ◽  
Vol 146 (9) ◽  
pp. 1109-1115 ◽  
Author(s):  
Robert P. Hirt
Keyword(s):  
Host Interactions ◽  
Detection Techniques ◽  
Symbiotic Relationships ◽  
Life Styles ◽  
Mucosal Surfaces ◽  
Microbe Interactions ◽  
Health And Disease ◽  
Host Microbe Interactions ◽  
Species Being

AbstractMicrobial parasites adapted to thrive at mammalian mucosal surfaces have evolved multiple times from phylogenetically distant lineages into various extracellular and intracellular life styles. Their symbiotic relationships can range from commensalism to parasitism and more recently some host–parasites interactions are thought to have evolved into mutualistic associations too. It is increasingly appreciated that this diversity of symbiotic outcomes is the product of a complex network of parasites–microbiota–host interactions. Refinement and broader use of DNA based detection techniques are providing increasing evidence of how common some mucosal microbial parasites are and their host range, with some species being able to swap hosts, including from farm and pet animals to humans. A selection of examples will illustrate the zoonotic potential for a number of microbial parasites and how some species can be either disruptive or beneficial nodes in the complex networks of host–microbe interactions disrupting or maintaining mucosal homoeostasis. It will be argued that mucosal microbial parasitic diversity will represent an important resource to help us dissect through comparative studies the role of host–microbe interactions in both human health and disease.

The role of the immune system in governing host-microbe interactions in the intestine

2013 ◽  
Vol 14 (7) ◽  
pp. 660-667 ◽  
Author(s):  
Eric M Brown ◽  
Manish Sadarangani ◽  
B Brett Finlay
Keyword(s):  
Immune System ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Expression of heat shock proteins 27 and 72 correlates with specific commensal microbes in different regions of porcine gastrointestinal tract

2014 ◽  
Vol 306 (12) ◽  
pp. G1033-G1041 ◽  
Author(s):  
Hao-Yu Liu ◽  
Johan Dicksved ◽  
Torbjörn Lundh ◽  
Jan Erik Lindberg
Keyword(s):  
Immune System ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Bacterial Species ◽  
Host Immune System ◽  
Gi Tract ◽  
Microbe Interactions ◽  
Cell Type Specific ◽  
Host Microbe Interactions ◽  
Shock Proteins

The gastrointestinal (GI) tract of mammals is inhabited by trillions of microorganisms, resulting in exceedingly complex networking. The interaction between distinct bacterial species and the host immune system is essential in maintaining homeostasis in the gut ecosystem. For instance, the gut commensal microbiota dictates intestinal mucosa maturation and its abundant immune components, such as cytoprotective heat shock proteins (HSP). Here we examined physiological expression of HSP in the normal porcine GI tract and found it to be gut region- and cell type-specific in response to dietary components, microbes, and microbial metabolites to which the mucosa surface is exposed. Correlations between HSP72 expression and ileal Lactobacillus spp. and colonic clostridia species, and between HSP27 expression and uronic acid ingestion, were important interplays identified here. Thus this study provides novel insights into host-microbe interactions shaping the immune system that are modifiable by dietary regime.

scholarly journals Antivirulence Activity of the Human Gut Metabolome

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
L. Caetano M. Antunes ◽  
Julie A. K. McDonald ◽  
Kathleen Schroeter ◽  
Christian Carlucci ◽  
Rosana B. R. Ferreira ◽  
...  
Keyword(s):  
Small Molecules ◽  
Chemical Cues ◽  
Therapeutic Potential ◽  
Host Cells ◽  
Human Gut ◽  
Complex Ecosystem ◽  
Microbe Interactions ◽  
Health And Disease ◽  
Host Microbe Interactions

ABSTRACTThe mammalian gut contains a complex assembly of commensal microbes termed microbiota. Although much has been learned about the role of these microbes in health, the mechanisms underlying these functions are ill defined. We have recently shown that the mammalian gut contains thousands of small molecules, most of which are currently unidentified. Therefore, we hypothesized that these molecules function as chemical cues used by hosts and microbes during their interactions in health and disease. Thus, a search was initiated to identify molecules produced by the microbiota that are sensed by pathogens. We found that a secreted molecule produced by clostridia acts as a strong repressor ofSalmonellavirulence, obliterating expression of theSalmonellapathogenicity island 1 as well as host cell invasion. It has been known for decades that the microbiota protects its hosts from invading pathogens, and these data suggest that chemical sensing may be involved in this phenomenon. Further investigations should reveal the exact biological role of this molecule as well as its therapeutic potential.IMPORTANCEMicrobes can communicate through the production and sensing of small molecules. Within the complex ecosystem formed by commensal microbes living in and on the human body, it is likely that these molecular messages are used extensively during the interactions between different microbial species as well as with host cells. Deciphering such a molecular dialect will be fundamental to our understanding of host-microbe interactions in health and disease and may prove useful for the design of new therapeutic strategies that target these mechanisms of communication.

scholarly journals Guanylate-Binding Protein 1 Inhibits Nuclear Delivery of Kaposi's Sarcoma-Associated Herpesvirus Virions by Disrupting Formation of Actin Filament

2017 ◽  
Vol 91 (16) ◽  
Author(s):  
Zhe Zou ◽  
Zhihua Meng ◽  
Chao Ma ◽  
Deguang Liang ◽  
Rui Sun ◽  
...  
Keyword(s):  
Immune System ◽  
Actin Filaments ◽  
Primary Infection ◽  
Rna Viruses ◽  
Critical Role ◽  
Host Cells ◽  
Host Immune System ◽  
Kshv Infection ◽  
Guanylate Binding Protein

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is a typical gammaherpesvirus that establishes persistent lifelong infection in host cells. In order to establish successful infection, KSHV has evolved numerous immune evasion strategies to bypass or hijack the host immune system. However, host cells still produce immune cytokines abundantly during primary KSHV infection. Whether the immune effectors produced are able to inhibit viral infection and how KSHV successfully conquers these immune effectors remain largely unknown. The guanylate-binding protein 1 (GBP1) gene is an interferon-stimulated gene and exerts antiviral functions on several RNA viruses; however, its function in DNA virus infection is less well understood. In this study, we found that KSHV infection increases both the transcriptional and protein levels of GBP1 at the early stage of primary infection by activating the NF-κB pathway. The overexpression of GBP1 significantly inhibited KSHV infection, while the knockdown of GBP1 promoted KSHV infection. The GTPase activity and dimerization of GBP1 were demonstrated to be responsible for its anti-KSHV activity. Furthermore, we found that GBP1 inhibited the nuclear delivery of KSHV virions by disrupting the formation of actin filaments. Finally, we demonstrated that replication and transcription activator (RTA) promotes the degradation of GBP1 through a proteasome pathway. Taken together, these results provide a new understanding of the antiviral mechanism of GBP1, which possesses potent anti-KSHV activity, and suggest the critical role of RTA in the evasion of the innate immune response during primary infection by KSHV. IMPORTANCE GBP1 can be induced by various cytokines and exerts antiviral activities against several RNA viruses. Our study demonstrated that GBP1 can exert anti-KSHV function by inhibiting the nuclear delivery of KSHV virions via the disruption of actin filaments. Moreover, we found that KSHV RTA can promote the degradation of GBP1 through a proteasome-mediated pathway. Taken together, our results elucidate a novel mechanism of GBP1 anti-KSHV activity and emphasize the critical role of RTA in KSHV evasion of the host immune system during primary infection.

scholarly journals Gut mélange à trois: fluctuating selection modulated by microbiota, host immune system, and antibiotics

2021 ◽  
Author(s):  
Hugo Condessa Barreto ◽  
Beatriz Abreu ◽  
Isabel Gordo
Keyword(s):  
Immune System ◽  
Iron Homeostasis ◽  
Host Immune System ◽  
Iron Availability ◽  
Lipocalin 2 ◽  
Fluctuating Selection ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Iron is critical in host-microbe interactions, and its availability is under tight regulation in the mammalian gut. Antibiotics and inflammation are known to perturb iron availability in the gut, which could subsequently alter host-microbe interactions. Here, we show that an adaptive allele of iscR, encoding a major regulator of iron homeostasis of Escherichia coli, is under fluctuating selection in the mouse gut. In vivo competitions in immune-competent, immune-compromised, and germ-free mice reveal that the selective pressure on an iscR mutant E. coli is modulated by the presence of antibiotics, other members of the microbiota, and the immune system. In vitro assays show that iron availability is an important mediator of the iscR allele fitness benefits or costs. We identify Lipocalin-2, a host's innate immune system protein that prevents bacterial iron acquisition, as a major host mechanism underlying fluctuating selection of the iscR allele. Our results provide a remarkable example of strong fluctuating selection acting on bacterial iron regulation in the mammalian gut.

Early life: gut microbiota and immune development in infancy

2010 ◽  
Vol 1 (4) ◽  
pp. 367-382 ◽  
Author(s):  
R. Martin ◽  
A. Nauta ◽  
K. Ben Amor ◽  
L. Knippels ◽  
J. Knol ◽  
...  
Keyword(s):  
Immune System ◽  
Early Life ◽  
Fine Tuning ◽  
Host Immune System ◽  
Immune Development ◽  
Susceptibility To Infection ◽  
Age Dependent ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Mammalian Immune System

The immune system of infants is actively downregulated during pregnancy and therefore the first months of life represent a period of heightened susceptibility to infection. After birth, there is an age-dependent maturation of the immune system. Exposure to environmental microbial components is suggested to play an important role in the maturation process. The gastrointestinal tract is the major site of interaction between the host immune system and microorganisms, both commensal as well as potentially pathogenic. It is well established that the mammalian immune system is designed to help protect the host from invading microorganisms and other danger signals. However, recent research is emerging in the field of host-microbe interactions showing that commensal microorganisms (microbiota) are most likely one of the drivers of immune development and, in turn the immune system shapes the composition of the microbiota. Specific early microbial exposure of the gut is thought to dramatically reduce the incidence of inflammatory, autoimmune and atopic diseases further fuelling the scientific view that microbial colonisation plays an important role in regulating and fine-tuning the immune system throughout life. Therefore, the use of pre-, pro- and synbiotics may result in a beneficial microbiota composition that might have a pivotal role on the prevention of several important diseases that develop in early life such as necrotizing enterocolitis and atopic eczema.

scholarly journals Thioester-Containing Proteins in the Drosophila melanogaster Immune Response against the Pathogen Photorhabdus

Insects ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 85
Author(s):  
Ioannis Eleftherianos ◽  
Upasana Sachar
Keyword(s):  
Drosophila Melanogaster ◽  
Immune Surveillance ◽  
Fruit Fly ◽  
Research Field ◽  
Innate Immune ◽  
Host Immune System ◽  
Innate Immune Signaling ◽  
Microbe Interactions ◽  
Host Microbe Interactions

The fruit fly Drosophila melanogaster forms a magnificent model for interpreting conserved host innate immune signaling and functional processes in response to microbial assaults. In the broad research field of host-microbe interactions, model hosts are used in conjunction with a variety of pathogenic microorganisms to disentangle host immune system activities and microbial pathogenicity strategies. The pathogen Photorhabdus is considered an established model for analyzing bacterial virulence and symbiosis due to its unique life cycle that extends between two invertebrate hosts: an insect and a parasitic nematode. In recent years, particular focus has been given to the mechanistic participation of the D. melanogaster thioester-containing proteins (TEPs) in the overall immune capacity of the fly upon response against the pathogen Photorhabdus alone or in combination with its specific nematode vector Heterorhabditis bacteriophora. The original role of certain TEPs in the insect innate immune machinery was linked to the antibacterial and antiparasite reaction of the mosquito malaria vector Anopheles gambiae; however, revamped interest in the immune competence of these molecules has recently emerged from the D. melanogaster-Photorhabdus infection system. Here, we review the latest findings on this topic with the expectation that such information will refine our understanding of the evolutionary immune role of TEPs in host immune surveillance.

scholarly journals Xenorhabdus nematophilus as a Model for Host-Bacterium Interactions: rpoS Is Necessary for Mutualism with Nematodes

2001 ◽  
Vol 183 (16) ◽  
pp. 4687-4693 ◽  
Author(s):  
Eugenio I. Vivas ◽  
Heidi Goodrich-Blair
Keyword(s):  
Molecular Mechanisms ◽  
Host Bacterium ◽  
Gram Negative ◽  
Host Interactions ◽  
Specific Allele ◽  
Microbe Interactions ◽  
Xenorhabdus Nematophilus ◽  
Host Microbe Interactions ◽  
Wild Type Parent

ABSTRACT Xenorhabdus nematophilus, a gram-negative bacterium, is a mutualist of Steinernema carpocapsae nematodes and a pathogen of larval-stage insects. We use this organism as a model of host-microbe interactions to identify the functions bacteria require for mutualism, pathogenesis, or both. In many gram-negative bacteria, the transcription factor ςS controls regulons that can mediate stress resistance, survival, or host interactions. Therefore, we examined the role of ςS in the ability of X. nematophilus to interact with its hosts. We cloned, sequenced, and disrupted the X. nematophilus rpoS gene that encodes ςS. The X. nematophilus rpoS mutant pathogenized insects as well as its wild-type parent. However, therpoS mutant could not mutualistically colonize nematode intestines. To our knowledge, this is the first report of a specific allele that affects the ability of X. nematophilus to exist within nematode intestines, an important step in understanding the molecular mechanisms of this association.

scholarly journals Host–microbe interactions in the gut: lessons learned from models of inflammatory bowel diseases

2014 ◽  
Vol 1 (2) ◽  
pp. 61-76
Author(s):  
Eytan Wine
Keyword(s):  
Immune System ◽  
Animal Models ◽  
Patient Care ◽  
Inflammatory Bowel Diseases ◽  
Gut Microbes ◽  
Bowel Diseases ◽  
Microbe Interactions ◽  
Inflammatory Bowel ◽  
Host Microbe Interactions

The mammalian gut is the richest immune organ in the body and serves as a central location for immune system development, processing, and education. Inflammatory bowel diseases (IBD) provide excellent models for studying both innate and adaptive responses to gut microbes and the host-immune system – microbe interactions in the gut. Microbes are linked to almost all of the known disease-associated genetic polymorphisms in IBD and are critical mediators of environmental effects (through food, hygiene, and infection). Human and animal-based research supports the central role of microbes in IBD pathogenesis at multiple levels. Animal models of IBD only develop in the presence of microbes, and co-housing mice that are genetically susceptible to gut inflammation with normal mice can lead to the development of bowel injury. Recent advances in research technologies, such as deep-sequencing that enables detailed compositional analyses, have revolutionized the study of host–microbe interactions in the gut; however, knowing which bacteria are present in the bowel is likely not sufficient. The function of the microbiota as a community is recognized as a critical factor for gut homeostasis. Animal models of IBD have provided critical insight into basic biology and disease pathogenesis, especially regarding the role of microbes in IBD pathogenesis. Although many of these recent discoveries on host–microbe interactions are not yet applied to patient care, these basic observations will certainly revolutionize patient care in the future. Using such data, we may be able to predict risk of disease, define biological subtypes, establish tools for prevention, and even cure IBD using microbes or their products. A broad spectrum of therapeutic tools spanning from fecal transplantation, probiotics, prebiotics, and microbial products to microbe-tailored diets may supplement current IBD treatments.

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