Scavenger receptor CD204+ macrophages play an immunoregulatory role in hepatic viral infection (VIR1P.971)

Macrophages (MΦ) are important for the activation and direction of innate and adaptive immune responses, however their role in liver infection is particularly poorly understood, in part due to the presence of functionally distinct subsets within the population. The MΦ scavenger receptor CD204/SRA is a marker for alternatively activated (M2) MΦ, which have anti-inflammatory properties and participate in wound healing and tissue remodeling. To understand the function of CD204+ MΦ on regulating liver inflammation, we examined the activation and differentiation of MΦ in a murine model of hepatic viral infection. Our studies revealed that CD204 was upregulated on circulating and liver-resident MΦ following tail vein injection of adenovirus or MCMV. CD204+ macrophages appear to express high levels of PD-L1 and IL-10, suggesting an alteration of MΦ phenotype. Interestingly, virally infected CD204-deficient mice had less liver CD8+ T cells than their wild type counterparts and these T cells produced less IFNγ and granzyme B. In contrast, liver NK and NKT cell populations in knockout and WT mice were similar in size, but NK cells from CD204 deficient mice displayed increased granzyme B staining following infection. These data indicate that CD204+ MΦ play a critical role in modulating the immune response to hepatic viral infection.