Oral Passive Immunization With Plasma-Derived Polyreactive Secretory-Like IgA/M Partially Protects Mice Against Experimental Salmonellosis.

Blaise Corthésy,Alexander Schaub,Justine Monnerat,Cédric Vonarburg,Gilles Bioley,Marius Lötscher

doi:10.3389/fimmu.2018.02970

Blaise Corthésy, Alexander Schaub + Show 4 more

Open Access

https://doi.org/10.3389/fimmu.2018.02970

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Abstract

Secretory immunoglobulins have a critical role in defense of the gastrointestinal tract and are known to act by preventing bacterial acquisition. A stringent murine model of bacterial infection with Salmonella enterica Typhimurium was used to examine protection mediated by oral passive immunization with human plasma-derived polyreactive IgA and IgM antibodies (Abs) reconstituted as secretory-like immunoglobulins (SCIgA/M). This reagent has been shown to trigger Salmonella agglutination and to limit the entry of bacterium into intestinal Peyer's patches via immune exclusion. We now demonstrate that upon administration into ligated intestinal loops, SCIgA/M properly anchors in the mucus and is protected from degradation to a better extent that IgA/M or IgG. Moreover, prophylactic oral administration of SCIgA/M before intragastric infection of mice with a virulent strain of S. enterica Typhimurium allows to protect infected animals, as reflected by reduced colonization of both mucosal and systemic compartments, and conserved integrity of intestinal tissues. In comparison with IgA/M or IgG administration, SCIgA/M provided the highest degree of protection. Moreover, such protective efficacy is also observed after therapeutic oral delivery of SCIgA/M. Either prophylactic or therapeutic treatment with passively delivered SCIgA/M ensured survival of up to 50% of infected mice, while untreated animals all died. Our findings unravel the potential of oral passive immunization with plasma-derived polyreactive SCIgA/M Abs to fight gastrointestinal infections.

Highlights

Protection of mucosal surfaces against colonization and possible entry and invasion by microbes is provided by a combination of constitutive, non-specific substances, and by specific cellular and molecular immune mechanisms including secretory immunoglobulins (SIgs) [1, 2]
Using a stringent experimental mouse model of S. enterica Typhimurium (St) gut infection, we demonstrate that two prophylactic oral administrations of secretory-like IgA and IgM (SCIgA/M) given 8 and 24 h prior to infection with a lethal dose of St reduces tissue bacterial load and mortality rate more efficiently than polymeric plasma-derived polyreactive IgA and IgM (IgA/M) or IgG
Peyer’s patches (PPs), mesenteric lymph nodes (MLNs), spleen, and liver from mice orally administered SCIgA/M 1 h after oral infection. (B) Weight loss and disease scores determined at day 6 post-infection of mice treated therapeutically with SCIgA/M as in (A). (C,D) Same experiments as in (A,B) with infection performed with 2 × 106 St, followed by subsequent therapeutic oral administration of SCIgA/M 1 or 8 h after oral infection

Summary

Introduction

Protection of mucosal surfaces against colonization and possible entry and invasion by microbes is provided by a combination of constitutive, non-specific substances (mucus, lysozyme, and defensins), and by specific cellular and molecular immune mechanisms including secretory immunoglobulins (SIgs) [1, 2]. Experimental and clinical resistance to infection can be correlated with specific SIgA antibodies (Abs) serving as an immunological barrier at mucosal surfaces [3, 4]. They are produced by plasma cells in the basolateral part of the epithelium as dimeric. Mucosal Protection by Secretory-Like IgA/M molecules thanks to the presence of the J-chain. Presence of the J-chain on IgM allows for the binding of SC and the generation of SIgM that are released in the lumen to SIgA.

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