Toll-like receptors (TLRs), the key molecular sensors used by the mammalian innate immune system to detect microorganisms, were identified only in the late 1990s. These evolutionarily conserved receptors recognize pathogen associate molecular patterns, and their activation leads to an appropriate host-defense response. Tremendous progress has been made over the past few years in determining the role of TLRs in innate immunity. However we are still in an exponential phase of discovery about many important aspects of TLR biology. We have recently cloned a novel member of the mammalian Toll-like receptor (TLR) family, TLR13. TLR13 appears to activate only the MyD88-independent TRIF pathway, inducing type 1 interferon and inflammatory cytokines. Remarkably, TLR 13 seems able to recognize a viral molecular pattern, double-stranded RNA (dsRNA). We therefore hypothesize that TLR13 represents a novel member of the TLR family that plays a role in the recognition of dsRNA during viral infection to activate innate immune response. We will generate specific antibodies against TLR13 to determine the endogenous protein localization. We will study the pattern of expression of TLR13 and determine whether its cellular localization and level of expression are altered upon stimulation of cells with viral dsRNA as well as other inflammatory mediators. Then we will determine whether it cooperates with other members of the TLR family. Furthermore we will clarify and determine the signaling pathways activated by TLR13. Finally we will generate a TLR13 knock-out mouse to systematically analyze the biological role of TLR13. ? ? ? ?
| Cai, Zhenyu; Shi, Zhongcheng; Sanchez, Amir et al. (2009) Transcriptional regulation of Tlr11 gene expression in epithelial cells. J Biol Chem 284:33088-96 |
| Shi, Zhongcheng; Cai, Zhenyu; Wen, Shu et al. (2009) Transcriptional regulation of the novel Toll-like receptor Tlr13. J Biol Chem 284:20540-7 |
