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

The ability of coronaviruses to induce an interferon response in some cells and not others is not well understood. BMM and BMDC are derived from the same BM progenitor cells in the presence of different cytokines, but they show substantial differences in type I IFN production and in cytokine and chemokine profiles (41, 44) . Here, we show that maximal IFN production in murine coronavirusinfected BMM requires signaling through the IFNAR (Fig. 3C) . We could detect small amounts of IFN mRNA but not protein in MHVinfected BMM at 8 h p.i. (Fig. 1) . However, IFN may have been produced at low levels at this early time p.i. but immediately depleted by binding to the IFNAR. In support of this, in a prior study, basal expression of IFN by BMM was detected when IFNAR Ϫ/Ϫ but not WT BMM were examined by an ELISA (41) . Together, these results suggest that a very small amount of IFN produced initially following infection effected a large increase in the levels of IFN and other inflammatory molecules via autocrine signaling. However, treatment of uninfected BMM with exogenous IFN did not induce the same level of expression of some of these molecules as occurred in MHVinfected cells at 16 h p.i. (Fig. 6) . Thus, active virus replication induced cytokine and chemokine expression via additional pathways in BMM. Furthermore, these molecules were largely produced by infected cells and not neighboring uninfected cells.