scholarly journals The Role of the Polymeric Immunoglobulin Receptor and Secretory Immunoglobulins during Mucosal Infection and Immunity

Viruses ◽  
2018 ◽  
Vol 10 (5) ◽  
pp. 237 ◽  
Author(s):  
Holly Turula ◽  
Christiane Wobus
Keyword(s):  
Polymeric Immunoglobulin Receptor ◽  
Immunoglobulin Receptor ◽  
Mucosal Infection ◽  
Secretory Immunoglobulins

scholarly journals Natural Secretory Immunoglobulins Promote Enteric Viral Infections

2018 ◽  
Vol 92 (23) ◽  
Author(s):  
Holly Turula ◽  
Juliana Bragazzi Cunha ◽  
Bernardo A. Mainou ◽  
Sadeesh K. Ramakrishnan ◽  
Carol A. Wilke ◽  
...  
Keyword(s):  
Enteric Virus ◽  
Enteric Pathogens ◽  
Polymeric Immunoglobulin Receptor ◽  
Murine Norovirus ◽  
Virus Infections ◽  
Significant Morbidity ◽  
Immunoglobulin Receptor ◽  
Ifn Γ ◽  
Secretory Immunoglobulins

ABSTRACTNoroviruses are enteric pathogens causing significant morbidity, mortality, and economic losses worldwide. Secretory immunoglobulins (sIg) are a first line of mucosal defense against enteric pathogens. They are secreted into the intestinal lumen via the polymeric immunoglobulin receptor (pIgR), where they bind to antigens. However, whether natural sIg protect against norovirus infection remains unknown. To determine if natural sIg alter murine norovirus (MNV) pathogenesis, we infected pIgR knockout (KO) mice, which lack sIg in mucosal secretions. Acute MNV infection was significantly reduced in pIgR KO mice compared to controls, despite increased MNV target cells in the Peyer's patch. Natural sIg did not alter MNV binding to the follicle-associated epithelium (FAE) or crossing of the FAE into the lymphoid follicle. Instead, naive pIgR KO mice had enhanced levels of the antiviral inflammatory molecules interferon gamma (IFN-γ) and inducible nitric oxide synthase (iNOS) in the ileum compared to controls. Strikingly, depletion of the intestinal microbiota in pIgR KO and control mice resulted in comparable IFN-γ and iNOS levels, as well as MNV infectious titers. IFN-γ treatment of wild-type (WT) mice and neutralization of IFN-γ in pIgR KO mice modulated MNV titers, implicating the antiviral cytokine in the phenotype. Reduced gastrointestinal infection in pIgR KO mice was also observed with another enteric virus, reovirus. Collectively, our findings suggest that natural sIg are not protective during enteric virus infection, but rather, that sIg promote enteric viral infection through alterations in microbial immune responses.IMPORTANCEEnteric virus, such as norovirus, infections cause significant morbidity and mortality worldwide. However, direct antiviral infection prevention strategies are limited. Blocking host entry and initiation of infection provides an established avenue for intervention. Here, we investigated the role of the polymeric immunoglobulin receptor (pIgR)-secretory immunoglobulin (sIg) cycle during enteric virus infections. The innate immune functions of sIg (agglutination, immune exclusion, neutralization, and expulsion) were not required during control of acute murine norovirus (MNV) infection. Instead, lack of pIgR resulted in increased IFN-γ levels, which contributed to reduced MNV titers. Another enteric virus, reovirus, also showed decreased infection in pIgR KO mice. Collectively, our data point to a model in which sIg-mediated microbial sensing promotes norovirus and reovirus infection. These data provide the first evidence of the proviral role of natural sIg during enteric virus infections and provide another example of how intestinal bacterial communities indirectly influence MNV pathogenesis.

Role of nuclear factor-??B in the expression by tumor necrosis factor-? of the human polymeric immunoglobulin receptor ( pIgR ?) gene

2000 ◽  
Vol 51 (4-5) ◽  
pp. 289-295 ◽  
Author(s):  
N. Takenouchi-Ohkubo ◽  
T. Takahashi ◽  
M. Tsuchiya ◽  
J. Mestecky ◽  
Z. Moldoveanu ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Polymeric Immunoglobulin Receptor ◽  
Nuclear Factor ◽  
Factor B ◽  
Immunoglobulin Receptor ◽  
Necrosis Factor

scholarly journals Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis

2021 ◽  
Vol 22 (5) ◽  
pp. 2284
Author(s):  
Hao Wei ◽  
Ji-Yang Wang
Keyword(s):  
Molecular Chaperone ◽  
Recent Progress ◽  
Marginal Zone ◽  
Specific Protein ◽  
Polymeric Immunoglobulin Receptor ◽  
Immunoglobulin Receptor ◽  
J Chain ◽  
Chaperone Protein ◽  
Apical Side

Transcytosis of polymeric IgA and IgM from the basolateral surface to the apical side of the epithelium and subsequent secretion into mucosal fluids are mediated by the polymeric immunoglobulin receptor (pIgR). Secreted IgA and IgM have vital roles in mucosal immunity in response to pathogenic infections. Binding and recognition of polymeric IgA and IgM by pIgR require the joining chain (J chain), a small protein essential in the formation and stabilization of polymeric Ig structures. Recent studies have identified marginal zone B and B1 cell-specific protein (MZB1) as a novel regulator of polymeric IgA and IgM formation. MZB1 might facilitate IgA and IgM transcytosis by promoting the binding of J chain to Ig. In this review, we discuss the roles of pIgR in transcytosis of IgA and IgM, the roles of J chain in the formation of polymeric IgA and IgM and recognition by pIgR, and focus particularly on recent progress in understanding the roles of MZB1, a molecular chaperone protein.

scholarly journals Dimerization of the Polymeric Immunoglobulin Receptor Controls Its Transcytotic Trafficking

1998 ◽  
Vol 9 (4) ◽  
pp. 901-915 ◽  
Author(s):  
Karen L. Singer ◽  
Keith E. Mostov
Keyword(s):  
Transmembrane Domain ◽  
Cell Receptor ◽  
Jurkat Cells ◽  
Glycophorin A ◽  
Polymeric Immunoglobulin Receptor ◽  
Receptor Dimerization ◽  
Immunoglobulin Receptor ◽  
Receptor Oligomerization ◽  
Necessary And Sufficient

Binding of dimeric immunoglobulin (Ig)A to the polymeric Ig receptor (pIgR) stimulates transcytosis of pIgR across epithelial cells. Through the generation of a series of pIgR chimeric constructs, we have tested the ability of ligand to promote receptor dimerization and the subsequent role of receptor dimerization on its intracellular trafficking. Using the cytoplasmic domain of the T cell receptor-ζ chain as a sensitive indicator of receptor oligomerization, we show that a pIgR:ζ chimeric receptor expressed in Jurkat cells initiates a ζ-specific signal transduction cascade when exposed to dimeric or tetrameric IgA, but not when exposed to monomeric IgA. In addition, we replaced the pIgR’s transmembrane domain with that of glycophorin A to force dimerization or with a mutant glycophorin transmembrane domain to prevent dimerization. Forcing dimerization stimulated transcytosis of the chimera, whereas preventing dimerization abolished ligand-stimulated transcytosis. We conclude that binding of dimeric IgA to the pIgR induces its dimerization and that this dimerization is necessary and sufficient to stimulate pIgR transcytosis.

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