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

MHV infection results in upregulation of IFN-dependent and -independent cytokines and chemokines to a greater extent in BMM than in BMDC. MHV infection induces expression of an array of cytokines and chemokines in the infected murine central nervous system (CNS), including CXCL10, CCL2 (chemokine [C-C motif] ligand 2), TNF, IL-6, IL-10, and IL-12, which play important roles in the anti-MHV immune response (39, 40) . We next examined whether BMM produced these cytokines and chemokines after MHV infection and, if so, whether their expression depended upon type I IFN production. We found that these genes were upregulated with similar kinetics in BMM and BMDC; however, BMM expressed much higher levels than BMDC did (Fig. 4A ) (data for IL-6 and IL-10 are not shown). These results were confirmed for TNF, CXCL10, and IL-12 p70 at the protein level by performing an enzyme-linked immunosorbent assay (ELISA) (Fig. 4C and D) . No IL-12 p70 mRNA or protein was detected in BMDC. Of note, basal mRNA levels of CXCL10 and TNF were higher in BMM than in BMDC, while the reverse was true for CCL2 (Fig. 4B) . Nevertheless, all three were expressed at higher levels in BMM during the peak time of infection (Fig. 4A) , indicating that the differences in basal levels did not explain the ability of BMM to produce larger amounts of inflammatory cytokines and chemokines in response to MHV infection.