Toll-like Receptor 11 (TLR11) Prevents Salmonella Penetration into the Murine Peyer Patches

作者:Shi Zhongcheng; Cai Zhenyu; Yu Jingcui; Zhang Tingting; Zhao Shu; Smeds Emanuel; Zhang Qingyuan; Wang Fen; Zhao Changhong; Fu Songbin; Ghosh Sankar; Zhang Dekai*
来源:JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287(52): 43417-43423.
DOI:10.1074/jbc.M112.411009

摘要

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-alpha 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.