LNCGM1082-mediated NLRC4 activation drives resistance to bacterial infection  

作　　者：Yunhuan Gao Yazheng Yang Jianmei Wei Jianmei Yue Ya Wang Qianjing Zhang Mengli Jin Rong Wang Xiaorong Yang Junqi Zhang Xinqi Liu Lin Liu Yuan Zhang Rongcun Yang 

机构地区：[1]Department of Immunology,Nankai University School of Medicine and Translational Medicine Institute,Affiliated Tianjin Union Medical Center of Nankai University,Nankai University,Tianjin 300071,China [2]State Key Laboratory of Medicinal Chemical Biology,Nankai University,Tianjin 300071,China [3]College of Life Science,Nankai University,Tianjin 300121,China [4]China National Center for Bioinformation&Bejing Institute of Genomics,Chinese Academy of Sciences,Bejing,China.

出　　处：《Cellular & Molecular Immunology》2023年第5期475-488,共14页中国免疫学杂志（英文版）

基　　金：NSFC grants(grant numbers 81901677,82271779,91842302,81970457,and 91629102);The Tianjin Science and Technology Commission(grant number,18JCZDJC35300);A Ministry of Science and Technology(grant number,2016YFC1303604);The State Key Laboratory of Medicinal Chemical Biology and the Fundamental Research Funds for the Central University,Nankai university(63191724).

摘　　要：The activation of NLRC4 is a major host response against intracellular bacteria infection.However,NLRC4 activation after a host senses diverse stimuli is difficult to understand.Here,we found that the IncRNA LNCGM1082 plays a critical role in the activation of NLRC4.LNCGM1082 in macrophages affects the maturation of interleukin(IL)-1βand pyroptotic cell death only after exposure to an NLRC4 ligand.Similar to NLRC4-/-mice,LNCGM1082-/-mice were highly sensitive to Salmonella Typhimurium(S.T)infection.LNCGM1082 deficiency in mouse or human macrophages inhibited IL-1βmaturation and pyroptosis.Mechanistically,LNCGM1082 induced the binding of PKCS with NLRC4 in both mice and humans.In contrast,NLRC4 did not bind PKCo in LNCGM1082-/-macrophages.The activity of the IncRNA LNCGM1082 induced by S.T may be mediated through TLR5 in the macrophages of both mice and humans.In summary,our data indicate that TLR5-mediated LNCGM1082 activity can promote the binding of PKC with NLRC4 to activate NLRC4 and induce resistance to bacterial infection.

关 键 词：MACROPHAGES INFLAMMASOME IncRNA Cell pyroptosis NLRC4 PKCΔ 

分 类 号：R392[医药卫生—免疫学]