FIGURE 11.

Schematic model of induction of IL27-dependent pro-inflammatory and antiviral response in CHIKV-infected MDMs. IL27 production in CHIKV-infected MDMs is dependent on two signaling pathways depending on the TLRs activation. An early signal dependent on recognition of CHIKV-PAMPs by TLR1/2-MyD88 to activate NF-κB-complex and induce EBI3 mRNA expression (A); and a late signal dependent on recognition of intermediates of CHIKV replication by TLR3-TRIF, to activate IRF1 and induces IL27p28 mRNA expression (B). Both signals are required to produce a functional IL27 protein and activated IL27 signaling pathway involved in the induction of ISGs expression, including AVPs, cytokines, CC- and CXC- chemokines; to control CHIKV replication in human MDMs, in an IFN-independent manner (C). Activation of TLR4, by LPS, induces a high expression of both IL27 subunits in human MDMs and murine BMDM and activated robust STAT1-dependent pro-inflammatory and antiviral response in an IL27-dependent manner (D).