Differential Effects of Prostaglandin D(2) Signaling on Macrophages and Microglia in Murine Coronavirus Encephalomyelitis

Microglia and macrophages initiate and orchestrate the innate immune response to central nervous system (CNS) virus infections. Microglia initiate neurotropic coronavirus clearance from the CNS, but the role of infiltrating macrophages is not well understood. Here, using mice lacking cell-specific expression of DP1, the receptor for prostaglandin D(2) (PGD(2)), we delineate the relative roles of PGD(2) signaling in microglia and macrophages in murine coronavirus-infected mice. We show that the absence of PGD(2)/DP1 signaling on microglia recapitulated the suboptimal immune response observed in global DP1(−/−) mice. Unexpectedly, the absence of the DP1 receptor on macrophages had an opposite effect, resulting in enhanced activation and more rapid virus clearance. However, microglia are still required for disease resolution, even when macrophages are highly activated, in part because they are required for macrophage recruitment to sites of infection. Together, these results identify key differences in the effects of PGD(2)/DP1 signaling on microglia and macrophages and illustrate the complex relationship between the two types of myeloid cells.