A specific role for TLR1 in protective T(H)17 immunity during mucosal infection.
The balance between regulatory and inflammatory immune responses is critical to maintain intestinal homeostasis. Furthermore, the nature of the inflammatory response needs to be tailored to the tissue to provide proper protective immunity while preserving host integrity. TLR2 (Toll-like receptor 2) is a unique TLR in that it has been shown to promote regulatory and inflammatory T cell responses. Using Yersinia enterocolitica, we show that oral infection promotes T(H)17 immunity, whereas systemic infection promotes T(H)1 immunity. Furthermore, induction of T(H)17 immunity during oral infection is dependent on TLR1 and results from the combinatorial effect of TLR2/TLR1-induced IL-6 and IL-23 and the presence of TGF-β in the intestinal environment. Interestingly, TLR2/TLR1 was not involved in T(H)1 immune responses during systemic infection, whereas the TLR2/TLR6 receptor complex induced IL-10(+) regulatory T cell responses during both systemic and oral infections. Our results reveal that the route of infection is central in determining which pathways provide protective immunity. Furthermore, they also demonstrate that TLR2 has dual immune functions in the gut and identify TLR1 as a critical innate receptor for protective intestinal T(H)17 immunity.
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. depaolo@usc.edu
R William
RW
DePaolo
Karishma
K
Kamdar
Samira
S
Khakpour
Yui
Y
Sugiura
Wenxia
W
Wang
Bana
B
Jabri
D000818:Animals; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D051194:Toll-Like Receptor 1 / Q000276:immunology* / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D015009:Yersinia Infections / Q000276:immunology* / Q000378:metabolism; D015008:Yersinia enterocolitica / Q000276:immunology*
D053759:Interleukin-23; D015850:Interleukin-6; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10