4月10日,，國(guó)際著名雜志Cell Research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成果“NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens,，”,。
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(shí)別受體來識(shí)別病毒或細(xì)菌等外來病原體。Nod樣受體(NLR)是近年來研究發(fā)現(xiàn)的識(shí)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(gè)成員,，其生理學(xué)功能一直不清楚。
該工作主要由博士生姚依昆和王亞龍?jiān)阱X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(dá)，進(jìn)而影響胞內(nèi)病原菌(李斯特菌,，L. monocytogenes)特異性CD8＋ T細(xì)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(jī)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(guó)家自然科學(xué)基金委、國(guó)家科技部,、中國(guó)科學(xué)院和上海市科委等經(jīng)費(fèi)資助,。（生物谷Bioon.com）
doi:10.1038/cr.2012.56
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NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens
Yikun Yao1,*, Yalong Wang1,*, Fuxiang Chen2, Yin Huang1, Shu Zhu1, Qibin Leng3, Hongyan Wang4, Yufang Shi1 and Youcun Qian1
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.
