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...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.展开更多
基金NSFC grants(grant numbers 81901677,82271779,91842302,81970457,and 91629102)The Tianjin Science and Technology Commission(grant number,18JCZDJC35300)+1 种基金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).
文摘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.
