Autocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection

Zhou, Haixia; Zhao, Jincun; Perlman, Stanley

While a type I IFN amplification loop is critical for maximal production of IFN and other molecules such as CXCL10, some aspects of the innate response in MHV-infected BMM are not IFN dependent. Thus, expression of TNF, IL-12, and IL-6 ( Fig. 5) is completely dependent upon signaling through MyD88. MyD88 is a key adaptor molecule in signaling pathways used by IL-1, IL-18, and all of the TLRs except TLR3. We examined the expression of TLR2, -3, -4, -6, and -7 and found that they were expressed at low levels in uninfected BMM and upregulated after MHV infection (data not shown). Therefore, signaling through one of these molecules could initiate the expression of these MyD88-dependent cytokines. In fact, IL-6 and TNF production in peritoneal macrophages infected with the hepatotropic MHV-3 strain is TLR2 dependent (47) . However, in preliminary experiments, we detected the same levels of TNF and IL-6 in MHV-A59-infected B6 and TLR2 Ϫ/Ϫ BMM, suggesting that TLR2 does not have the same critical role in BMM as observed in MHV-3infected peritoneal macrophages. Consistent with this putative cellspecific difference in expression, splenic macrophages but not BMM produce TNF in response to TLR2 ligands (48) .