Natural Secretory Immunoglobulins Promote Enteric Viral Infections

Turula, Holly; Cunha, Juliana Bragazzi; Mainou, Bernardo A.; Ramakrishnan, S; Wilke, Carol A.; Gonzalez-Hernandez, Mariam B.; Pry, Alexandra; Fava, Julianne; Bassis, Christine M.; Edelman, Jacob; Shah, Yatrik M.; Corthésy, Blaise; Moore, Bethany B.; Wobus, Christiane E.

doi:10.1128/jvi.00826-18

Cited by 17 publications

(18 citation statements)

References 94 publications

(112 reference statements)

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“…It was suggested that the less diversified intestinal microbiota present in pIgR deficient mice was responsible for reduced infection. pIgR deficient mice had enhanced levels of the anti-viral cytokine IFN-γ, which might explain the reduced infection rates (109).…”

Section: Iga and Fcαri Mediated Functions At Different Locationsmentioning

confidence: 99%

IgA and FcαRI: Pathological Roles and Therapeutic Opportunities

2019

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Immunoglobulin A (IgA) is the most abundant antibody class present at mucosal surfaces. The production of IgA exceeds the production of all other antibodies combined, supporting its prominent role in host-pathogen defense. IgA closely interacts with the intestinal microbiota to enhance its diversity, and IgA has a passive protective role via immune exclusion. Additionally, inhibitory ITAMi signaling via the IgA Fc receptor (FcαRI; CD89) by monomeric IgA may play a role in maintaining homeostatic conditions. By contrast, IgA immune complexes (e.g., opsonized pathogens) potently activate immune cells via cross-linking FcαRI, thereby inducing pro-inflammatory responses resulting in elimination of pathogens. The importance of IgA in removal of pathogens is emphasized by the fact that several pathogens developed mechanisms to break down IgA or evade FcαRI-mediated activation of immune cells. Augmented or aberrant presence of IgA immune complexes can result in excessive neutrophil activation, potentially leading to severe tissue damage in multiple inflammatory, or autoimmune diseases. Influencing IgA or FcαRI-mediated functions therefore provides several therapeutic possibilities. On the one hand (passive) IgA vaccination strategies can be developed for protection against infections. Furthermore, IgA monoclonal antibodies that are directed against tumor antigens may be effective as cancer treatment. On the other hand, induction of ITAMi signaling via FcαRI may reduce allergy or inflammation, whereas blocking FcαRI with monoclonal antibodies, or peptides may resolve IgA-induced tissue damage. In this review both (patho)physiological roles as well as therapeutic possibilities of the IgA-FcαRI axis are addressed.

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Section: Iga and Fcαri Mediated Functions At Different Locationsmentioning

confidence: 99%

IgA and FcαRI: Pathological Roles and Therapeutic Opportunities

2019

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“…Commensal bacteria can influence the production of secretory immunoglobulins (sIG), which are secreted into the intestinal lumen and act as the first line of mucosal defense against enteric pathogens [44]. Surprisingly, sIGs promote acute MNoV and reovirus infection through the regulation of IFNγ and inducible nitric oxide synthase (iNOS) levels in the gut [45]. Also, the antibody response to rotavirus infection is impaired by the presence of enteric bacteria [46] and the presence of bacteria can influence vaccine efficacy.…”

Section: Modulation Of Innate and Adaptive Immune Responses By The MImentioning

confidence: 99%

Virus interactions with bacteria: Partners in the infectious dance

Neu

Mainou

2020

PLoS Pathog

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The outcome of viral infection depends on the interplay between host factors and the environment. Host factors, like the expression of viral receptors, convey permissiveness to infection, define tropism, regulate antiviral immune responses, determine viral clearance, and spread. The host microbiota, the constellation of microbes inhabiting an organism, also plays a key role in the outcome of infection. Microbes and microbial products can directly interact with viral particles. Our understanding of how the microbiota impacts virus infection is largely limited to the bacterial component of the microbiota. Although bacteria do not support eukaryotic virus infection, they can promote viral fitness by enhancing virion stability, promoting infection of eukaryotic cells, and increasing coinfection rates. Virus binding of bacteria can also impact bacterial biology, including bacterial adherence to eukaryotic cells. These interactions can also indirectly affect the host response to viral infection. In this Pearl, we focus on how direct and indirect interactions between viruses and bacteria impact viral biology and touch on recent findings that illustrate how bacterial biology can also be impacted by interactions with eukaryotic viruses (Fig 1).

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“…Increases in IFN-γ, IL-2, TNF-α, MIP-1, and granzyme-B have been associated with the activation of cytotoxic T lymphocytes (CTLs), which were responsible for the lysis of infected cells [55,57,58]. Activated CD8+ T cells and increased IFN-λ in particular have significantly reduced viral loads and helped clear persistent MNV infection in mice [58,59,60]. Inefficient acquisition and maintenance of polyfunctional T cell capability with respect to cytokines, chemokines, and cytotoxic potential have been associated with persistent MNV infection [58].…”

Section: Adaptive Immunity To Norovirusesmentioning

confidence: 99%

The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics

Sels

Green

2019

Viruses

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Human norovirus (HuNoV) is the leading cause of acute nonbacterial gastroenteritis. Vaccine design has been confounded by the antigenic diversity of these viruses and a limited understanding of protective immunity. We reviewed 77 articles published since 1988 describing the isolation, function, and mapping of 307 unique monoclonal antibodies directed against B cell epitopes of human and murine noroviruses representing diverse Genogroups (G). Of these antibodies, 91, 153, 21, and 42 were reported as GI-specific, GII-specific, MNV GV-specific, and G cross-reactive, respectively. Our goal was to reconstruct the antigenic topology of noroviruses in relationship to mapped epitopes with potential for therapeutic use or inclusion in universal vaccines. Furthermore, we reviewed seven published studies of norovirus T cell epitopes that identified 18 unique peptide sequences with CD4- or CD8-stimulating activity. Both the protruding (P) and shell (S) domains of the major capsid protein VP1 contained B and T cell epitopes, with the majority of neutralizing and HBGA-blocking B cell epitopes mapping in or proximal to the surface-exposed P2 region of the P domain. The majority of broadly reactive B and T cell epitopes mapped to the S and P1 arm of the P domain. Taken together, this atlas of mapped B and T cell epitopes offers insight into the promises and challenges of designing universal vaccines and immunotherapy for the noroviruses.

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Natural Secretory Immunoglobulins Promote Enteric Viral Infections

Cited by 17 publications

References 94 publications

IgA and FcαRI: Pathological Roles and Therapeutic Opportunities

IgA and FcαRI: Pathological Roles and Therapeutic Opportunities

Virus interactions with bacteria: Partners in the infectious dance

The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics

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