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

  1. Dekai Zhang,1
  1. From the Center for Infectious and Inflammatory Diseases and
  2. Center for Cancer and Stem Cell Biology at the Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas 77030,
  3. the Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University and
  4. the §Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China, and
  5. the **Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York 10032
  1. 1 To whom correspondence should be addressed. Tel.: 713-677-7565; Fax: 713-677-7576; E-mail: dzhang{at}ibt.tamhsc.edu.

Background: The role of different TLRs in response to pathogen infection in the gut remains elusive.

Results: TLR11 works as a blocker of Salmonella penetration. Remarkably, in mice lacking TLR11, highly invasive Salmonella induced apparent hemorrhage at Peyer patches.

Conclusion: TLR11 plays an important role in preventing murine intestinal infection.

Significance: TLR11 knock-out mice can serve as a good animal model to study Salmonella infection.

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.

Footnotes

  • * This work was supported, in whole or in part, by National Institutes of Health Grant 1R56AI085164. This work was also supported by the Texas A&M University Health Science Center.

  • Received August 16, 2012.
  • Revision received November 4, 2012.
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This Article

  1. The Journal of Biological Chemistry 287, 43417-43423.
  1. All Versions of this Article:
    1. M112.411009v1
    2. 287/52/43417 (most recent)

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