Enhanced survival following oral and systemic Salmonella enterica serovar Typhimurium infection in polymeric immunoglobulin receptor knockout mice

Abstract

BackgroundPolymeric immunoglobulin receptor (pIgR) transport of secretory immunoglobulin A (SIgA) to mucosal surfaces is thought to promote gut integrity and immunity to Salmonella enterica serovar Typhimurium (S. Typhimurium), an invasive pathogen in mice. To elucidate potential mechanisms, we assessed intestinal barrier function and both oral and systemic S. Typhimurium virulence in pIgR knockout (KO) and wildtype (WT) mice.MethodsIn uninfected animals, we harvested jejunal segments for Ussing chamber analyses of transepithelial resistance (TER); mesenteric lymph nodes (mLN) for bacterial culture; and serum and stool for IgA. Separately, we infected mice either orally or intravenously (IV) with S. Typhimurium to compare colonization, tissue dynamics, and inflammation between KOs and WTs.ResultsUninfected KOs displayed decreased TER and dramatically increased serum IgA and decreased fecal IgA vs. WT; however, KO mLNs yielded fewer bacterial counts. Remarkably, WTs challenged orally with S. Typhimurium exhibited increased splenomegaly, tissue colonization, and pro-inflammatory cytokines vs. pIgR KOs, which showed increased survival following either oral or IV infection.ConclusionsAbsence of pIgR compromises gut integrity but does not exacerbate bacterial translocation nor S. Typhimurium infection. These findings raise the possibility that immune adaptation to increased gut permeability and elevated serum IgA in the setting of SIgA deficiency provides compensatory protection against invasive gut pathogens.

Pathological and Immunohistochemical Assessment of Salmonellatyphimurium Pathogenicity During Oral Experimental Infection in Mice

“…Further serological research to compare between pIgR knockout mice and wildtype mice was done to detect both IgA and IgG in the sera samples and stool specimens in response to oral dosing and intravenous injection of pathogenic S. typhimurium. The concentration of IgA and IgG measured by ELISA demonstrated significant increase of IgA and IgG (P<0.05) in the sera of pIgR knockout mice by comparison with the wildtype mice which resulted in elevation of survival rates in these mice against S. typhimurium infection 46 with which we agree.…”

Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis

“…This was directly confirmed by comparing the intestinal microbiota between pIgR −/− and WT mice using 16s rRNA analysis [ 81 ]. Intestinal integrity was mildly compromised in pIgR −/− mice, which might be attributed to a slightly more severe bacterial insult in pIgR −/− mice [ 82 , 83 ]. This may explain the results from an early study, which showed that pIgR −/− mice were profoundly more sensitive to infection with Salmonella typhimurium via the fecal-oral route, and that bacteria excreted from pIgR −/− mice after S. typhimurium infection were more contagious for other mice [ 84 ], as the composition of the excreted bacterial population may differ between pIgR −/− and WT mice.…”

Immunoglobulin A, an Active Liaison for Host-Microbiota Homeostasis

“…While these recombinant monoclonal antibodies signify the bactericidal ability of SIgA, there are conflicting reports as to whether innate SIgA confers protection against STm. In two independent reports, pIgR-deficient mice were infected with STm SL1344 at either a dose of 10 9 CFU or 10 7 CFU, respectively, where the first group demonstrated increased survival and protection from systemic dissemination of STm, but the second group had more profound infection [252,253]. It is noteworthy, though, that previously immunized pIgR-deficient mice and their wild-type litter mates were equally resistant to STm challenge [254].…”