真核生物的天然免疫是抵抗外界病原體入侵的第一道防線。天然免疫主要是通過模式識別受體來識別病毒或細菌等外來病原體。Nod樣受體（NLR）是近年來研究發(fā)現(xiàn)的識別胞內(nèi)菌的模式受體,。NLRC5作為Nod樣受體家族中最大的一個成員，其生理學(xué)功能一直不清楚,。
4月10號,，Cell Research雜志在線發(fā)表中科院上海生命科學(xué)研究院/上海交通大學(xué)醫(yī)學(xué)院健康科學(xué)研究所錢友存研究組關(guān)于NLRC5在抗胞內(nèi)菌感染過程中的作用研究 (NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens)。該工作主要由博士生姚依昆和王亞龍在錢友存研究員的指導(dǎo)下完成,。該論文首次利用NLRC5基因敲除小鼠研究發(fā)現(xiàn)NLRC5在宿主抵抗胞內(nèi)菌感染方面發(fā)揮重要作用,。NLRC5通過調(diào)控I類主要組織相容性復(fù)合體（MHC class I）的轉(zhuǎn)錄表達，進而影響胞內(nèi)病原菌（李斯特菌,，L. monocytogenes）特異性CD8＋ T細胞的激活和增殖,，從而有效清除病原菌。該研究闡明了宿主抗胞內(nèi)菌感染的新機制,，為感染性疾病的預(yù)防與治療提供了重要的理論基礎(chǔ),。
該課題獲得國家自然科學(xué)基金委、國家科技部,、中國科學(xué)院和上海市科委等經(jīng)費資助,。(生物谷：Bioon.com)
doi:10.1038/cr.2012.56
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PMID:
NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens
Yikun Yao, Yalong Wang, Fuxiang Chen, Yin Huang, Shu Zhu, Qibin Leng, Hongyan Wang, Yufang Shi and Youcun Qian
NOD-like receptors (NLRs) are a family of intracellular proteins that play critical roles in innate immunity against microbial infection. NLRC5, the largest member of the NLR family, has recently attracted much attention. However, in vitro studies have reported inconsistent results about the roles of NLRC5 in host defense and in regulating immune signaling pathways. The in vivo function of NLRC5 remains unknown. Here, we report that NLRC5 is a critical regulator of host defense against intracellular pathogens in vivo. NLRC5 was specifically required for the expression of genes involved in MHC class I antigen presentation. NLRC5-deficient mice showed a profound defect in the expression of MHC class I genes and a concomitant failure to activate L. monocytogenes-specific CD8+ T cell responses, including activation, proliferation and cytotoxicity, and the mutant mice were more susceptible to the pathogen infection. NLRP3-mediated inflammasome activation was also partially impaired in NLRC5-deficient mice. However, NLRC5 was dispensable for pathogen-induced expression of NF-κB-dependent pro-inflammatory genes as well as type I interferon genes. Thus, NLRC5 critically regulates MHC class I antigen presentation to control intracellular pathogen infection.
