Abstract

Toll-like receptors (TLRs) are key molecular sensors used by the mammalian innate immune system to detect microorganisms. Although TLR functions in colonic immune homeostasis and tolerance to commensal bacteria have been intensively researched, the precise roles of different TLRs in response to pathogen infection in the gut remain elusive. Peyer patches are the major entrance of Salmonella infection and antigen transportation in intestine. Here, we report that, in contrast to TLR5 as a "carrier of Salmonella," TLR11 works as a "blocker of Salmonella" to prevent highly invasive Salmonella from penetrating into the murine Peyer patches and spreading systemically. TLR11 plays an important role in mediating TNF-α induction and systemic inflammation in response to Salmonella infection. Remarkably, in mice lacking TLR11, apparent hemorrhages at Peyer patches are induced by highly invasive Salmonella, a phenotype resembling human Salmonella infection. Therefore, our results indicate a potentially important role for TLR11 in preventing murine intestinal infection and modulating antigen transportation in the gut and imply an important role for various TLRs in cooperation with tight control of pathogens penetrating into Peyer patches. The TLR11 knock-out mouse can serve as a good animal model to study Salmonella infection.

Highlights

  • The role of different Toll-like receptors (TLRs) in response to pathogen infection in the gut remains elusive

  • Bleeding of Peyer Patches in TLR11Ϫ/Ϫ Mice after Salmonella Infection—We realized that TLR11 is expressed in the epithelial cell in the urinary tract and in the gastrointestinal tract [17]; we investigated the role of TLR11 in Salmonella infection by using its knock-out mouse

  • Because the Peyer patches are the main portal of entry for invasive enteric Salmonella infections [19, 20], we wanted first to determine whether there is a bacterial load difference between the wild-type and TLR11-deficient mice in this organ

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Summary

Background

The role of different TLRs in response to pathogen infection in the gut remains elusive. TLR functions in colonic immune homeostasis and tolerance to commensal bacteria have been intensively researched, the precise roles of different TLRs in response to pathogen infection in the gut remain elusive. Our results indicate a potentially important role for TLR11 in preventing murine intestinal infection and modulating antigen transportation in the gut and imply an important role for various TLRs in cooperation with tight control of pathogens penetrating into Peyer patches. In contrast to the role of TLRs in colonic homeostasis and tolerance to commensal bacteria, the precise role of different TLRs in response to pathogen infection in different organs such as the intestine is still unclear [8, 12]. With the consideration that the bacteria in the urinary tract infection are mainly from gastrointestinal tract, we investigate the role of TLR11 in murine Salmonella infection

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