Reconstituted Human Polyclonal Plasma-derived Secretory-like IgM and IgA Maintain the Barrier Function of Epithelial Cells Infected with an Enteropathogen

Longet, Stéphanie; Vonarburg, Cédric; Lötscher, Marius; Miescher, Sylvia; Zuercher, Adrian W.; Corthésy, Blaise

doi:10.1074/jbc.m114.549139

Cited by 24 publications

(28 citation statements)

References 51 publications

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“…Intestinal IgM is able to bind bacteria (van der Waaij et al., ). IgM protects intestinal epithelial cells from Shigella flexneri in vitro, and the protective effect was higher than that of IgA (Longet et al., ). A different compensatory and protective mechanism is induced in MUC2‐deficient mice after chronic EtOH administration.…”

Section: Discussionmentioning

confidence: 99%

Genetic Loss of Immunoglobulin A Does Not Influence Development of Alcoholic Steatohepatitis in Mice

Inamine

Yang

Wang

et al. 2016

Alcoholism Clin & Exp Res

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Background Chronic alcohol abuse is associated with intestinal dysbiosis and bacterial translocation. Translocated commensal bacteria contribute to alcoholic liver disease. Secretory immunoglobulin A (IgA) in the intestine binds bacteria and prevents bacterial translocation. Aim To investigate the functional role of IgA in ethanol-induced liver disease in mice. Methods We subjected wild-type (WT) and IgA-deficient littermate mice to Lieber DeCarli models of chronic ethanol administration and the model of chronic and binge ethanol feeding (the NIAAA model). Results Chronic ethanol feeding increased systemic levels of IgA, while fecal IgA was reduced in C57BL/6 WT mice. WT and Iga−/− littermate mice showed similar liver injury, steatosis and inflammation following 4 weeks of ethanol feeding or chronic and binge ethanol feeding. IgA deficiency did not affect intestinal absorption or hepatic metabolism of ethanol. Pretreatment with ampicillin elevated intestinal IgA in WT littermate mice. Despite increased intestinal IgA, WT littermate mice exhibited a similar degree of liver disease compared with Iga−/− mice after 7 weeks of ethanol feeding. Interestingly, bacterial translocation to mesenteric lymph nodes was increased in Iga−/− mice fed an isocaloric diet, but was the same after ethanol feeding relative to WT littermate mice. The absence of intestinal IgA was associated with increased intestinal and plasma IgM in Iga−/− mice after ethanol feeding. Conclusions Our findings indicate that absence of IgA does not affect development of alcoholic liver disease in mice. Loss of intestinal IgA is compensated by increased levels of intestinal IgM, which likely limits bacterial translocation after chronic ethanol administration.

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Section: Discussionmentioning

confidence: 99%

Genetic Loss of Immunoglobulin A Does Not Influence Development of Alcoholic Steatohepatitis in Mice

Inamine

Yang

Wang

et al. 2016

Alcoholism Clin & Exp Res

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“…To examine the biding capacity of human plasma antibodies to bacteria ( 13 ), 96 well plates (Maxi-Sorp, Nunc) were coated with 4 × 10 7 cfu/well of St in PBS O/N at 4°C, prior to blocking with PBS-T containing 5% nonfat dry milk (NFDM). Serial dilutions of human plasma-derived monomeric IgA (mIgA) ( 9 ), pIgA, SIgA, IgM, SIgM, IgA/M, SCIgA/M, or IgG (starting at 0.5 µM) or SC (starting at 6.25 µM) were added.…”

Section: Methodsmentioning

confidence: 99%

“…Polyreactive secretory-like IgA (SCIgA) and secretory-like IgM (SCIgM) antibodies reconstituted from plasma-derived polymeric immunoglobulins and SC ( 12 ), when associated with the enteropathogen Shigella flexneri , have proven to delay infection of polarized epithelial cell monolayers used as a surrogate of the intestinal barrier ( 13 ). However, in the in vivo context, it has to be determined whether polyreactive plasma-derived SCIgA and SCIgM antibodies have the potential to counteract the damaging effect of enteropathogens.…”

Section: Introductionmentioning

confidence: 99%

Plasma-Derived Polyreactive Secretory-Like IgA and IgM Opsonizing Salmonella enterica Typhimurium Reduces Invasion and Gut Tissue Inflammation through Agglutination

et al. 2017

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Due to the increasing emergence of antibiotic-resistant strains of enteropathogenic bacteria, development of alternative treatments to fight against gut infections is a major health issue. While vaccination requires that a proper combination of antigen, adjuvant, and delivery route is defined to elicit protective immunity at mucosae, oral delivery of directly active antibody preparations, referred to as passive immunization, sounds like a valuable alternative. Along the gut, the strategy suffers, however, from the difficulty to obtain sufficient amounts of antibodies with the appropriate specificity and molecular structure for mucosal delivery. Physiologically, at the antibody level, the protection of gastrointestinal mucosal surfaces against enteropathogens is principally mediated by secretory IgA and secretory IgM. We previously demonstrated that purified human plasma-derived IgA and IgM can be associated with secretory component to generate biologically active secretory-like IgA and IgM (SCIgA/M) that can protect epithelial cells from infection by Shigella flexneri in vitro. In this study, we aimed at evaluating the protective potential of these antibody preparations in vivo. We now establish that such polyreactive preparations bind efficiently to Salmonella enterica Typhimurium and trigger bacterial agglutination, as observed by laser scanning confocal microscopy. Upon delivery into a mouse ligated intestinal loop, SCIgA/M-mediated aggregates persist in the intestinal environment and limit the entry of bacteria into intestinal Peyer’s patches via immune exclusion. Moreover, oral administration to mice of immune complexes composed of S. Typhimurium and SCIgA/M reduces mucosal infection, systemic dissemination, and local inflammation. Altogether, our data provide valuable clues for the future appraisal of passive oral administration of polyreactive plasma-derived SCIgA/M to combat infection by a variety of enteropathogens.

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“…47 In an experimental Shigella flexneri mouse model, sIgM also displayed the ability to modulate the expression of bacterial virulence factors, thereby preserving epithelial surface homeostasis. 48 Unlike sIgA, sIgM can activate the complement system, facilitating pathogen killing through the classical pathway and leading to membrane attack complex formation or opsonisation for phagocytosis. Kirkland et al demonstrated that sIgM-and complement-deficiency are associated with a worse disease course of DSS-induced colitis, supporting a role for IgM in intestinal homeostasis.…”

Section: Secretory Igm Reinforces the Role Of Secretory Igamentioning

confidence: 99%

The antibody/microbiota interface in health and disease

et al. 2020

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The human intestine is densely colonized with commensal microbes that stimulate the immune system. While secretory Immunoglobulin (Ig) A is known to play a crucial role in gut microbiota compartmentalization, secretory IgM, and systemic IgG have recently been highlighted in host-microbiota interactions as well. In this review, we discuss important aspects of secretory IgA biology, but rather than focusing on mechanistic aspects of IgA impact on microbiota, we stress the current knowledge of systemic antibody responses to whole gut microbiota, in particular their generation, specificities, and function. We also provide a comprehensive picture of secretory IgM biology. Finally, therapeutic and diagnostic implications of these novel findings for the treatment of various diseases are outlined.

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Reconstituted Human Polyclonal Plasma-derived Secretory-like IgM and IgA Maintain the Barrier Function of Epithelial Cells Infected with an Enteropathogen

Cited by 24 publications

References 51 publications

Genetic Loss of Immunoglobulin A Does Not Influence Development of Alcoholic Steatohepatitis in Mice

Genetic Loss of Immunoglobulin A Does Not Influence Development of Alcoholic Steatohepatitis in Mice

Plasma-Derived Polyreactive Secretory-Like IgA and IgM Opsonizing Salmonella enterica Typhimurium Reduces Invasion and Gut Tissue Inflammation through Agglutination

The antibody/microbiota interface in health and disease

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