Fig. 2

The signaling pathways for NLRs. Activated NLRC1 and NLRC2 respectively self-oligomerize, and then recruit RIPK2. RIPK2 not only activates TAK1 to induce IKK-NF-κB and MAPK-AP1 pathway, but also interacts with TRAF3 to induce TBK1-IKKε complex and further activates IRF7, which result in the transcription of proinflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) and type I IFNs, respectively. Once NLRC2 is activated by ssRNA of virus, NLRC2 oligomerizes and then interacts with MAVS protein and TRAF3 to activate IRF3 pathway, which induces expression of type I IFNs. Activated NLRC4/NAIP and NLRP members (NLRP1, 3, 6, 7 and 12) recruit ASCs and caspase-1 to form the basis of the inflammasome. The activated caspase-1 not only cleaves pro-IL-1β and pro-IL-18 into IL-1β and IL-18, but also triggers pyroptosis by cleaving GSDMD. So far, the downstream signaling pathways of NLRC3, NLRP10 and NLRX1 remain to be investigated