Initiation of mucosal innate immune response via dendritic cells against <i>Toxoplasma gondii</i> infection in mice.

<p>The toll-like receptor (TLR)-adaptor protein MyD88 is a key element to the protective response based on production of IL-12. Secretion of IL-12 will trigger an effective cellular-based immune response with production of INF-γ and activation of a Th1 T lymphocyte profile. (A) This innate response is mainly dependent on TLR11, which forms endolysosomal dimers with TLR12 that recognize profilin from <i>T</i>. <i>gondii</i>. This recognition is central to mucosal immunity triggering production of IL-12. (B) In the absence of TLR11, however, this response is still minimally and sufficiently compensated by indirect stimulation provided by the gut microbial commensals via TLR2, TLR4, and TLR9 [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004176#pntd.0004176.ref044" target="_blank">44</a>]. In this case, infection-induced cell destruction and intestinal dysbiosis apparently trigger loss of tolerance to gut commensals. When the gut microbiota is severely reduced by prolonged antibiotic treatment, the following observations can be made: (C) Wild-type mice expressing TLR11 exhibit a reduced but not abolished IL-12 response. These animals can still build up Th1 immunity. (D) TLR11-knockout mice are unable to mount IL-12 responses against this parasite, and Th1 immunity is severely impaired. In conclusion, gut commensals serve as natural molecular adjuvants during <i>T</i>. <i>gondii</i> infection.