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

Here, we cultured primary bone marrow (BM) cells in vitro in the presence of cytokines and growth factors, resulting in differentiation into cells with the characteristics of macrophages (BMM, cultured in the presence of macrophage colonystimulating factor [M-CSF]; CD11b ϩ CD11c Ϫ ) or dendritic cells (BMDC, cultured in the presence of granulocyte-macrophage colony-stimulating factor [GM-CSF] and interleukin-4 [IL-4]; CD11b ϩ CD11c ϩ ). Using these cells, we showed that most of the IFN produced after MHV infection was dependent on signaling through the IFN-␣/␤ receptor (IFNAR). This IFN was critical for virus-induced upregulation of several IFN-related molecules, including MDA5, RIG-I, and CXCL10 (chemokine [C-X-C motif] ligand 10). Further, levels of type I IFN produced in MHVinfected BMM were sufficient to induce maximal activation, since exogenous type I IFN treatment did not further stimulate IFNrelated gene upregulation at late times postinfection (p.i.). Our results also showed that the expression of some inflammationassociated molecules, most notably tumor necrosis factor (TNF), IL-12, and IL-6, was mediated, in large part, via signaling through myeloid differentiation factor 88 (MyD88)-dependent pathways.