J Biol Chem. 2010 Nov 19. [Epub ahead of print]
UNC93B1 is essential for TLR11 activation and IL-12 dependent host resistance to Toxoplasma gondii
Pifer R, Benson A, Sturge CR, Yarovinsky F.
University of Texas Southwestern Medical Center at Dallas, United States.
Toll-like receptor (TLR) activation relies on biochemical recognition of microbial molecules and localization of the TLR within specific cellular compartments. Cell surface TLRs largely recognize bacterial membrane components, and intracellular TLRs are exclusively involved in sensing nucleic acids. Here we show that TLR11, an innate sensor for the Toxoplasma protein profilin, is an intracellular receptor that resides in the endoplasmic reticulum. The twelve membrane-spanning endoplasmic reticulum-resident protein UNC93B1 interacts directly with TLR11 and regulates the activation of dendritic cells (DC) in response to T. gondii profilin and parasitic infection in vivo. A deficiency in functional UNC93B1 protein abolished TLR11-dependent IL-12 secretion by DC, attenuated Th1 responses against T. gondii, and dramatically enhanced susceptibility to the parasite. Our results reveal that the association with UNC93B1 and the intracellular localization of TLRs is not a unique feature of nucleic acid-sensing TLRs but is also essential for TLR11-dependent recognition of T. gondii profilin and for host protection against this parasite.
PMID: 21097503 [PubMed - as supplied by publisher]