Functional heterogeneity of monocyte populations during influenza virus infection (P4243)

Abstract

Abstract Influenza infection in mice is characterized by waves of recruitment of innate immune cells into the lung. We have previously described TNF-α/iNOS-producing monocytes (TipDC) as promoting the anti-influenza adaptive immune response and contributing to disease pathogenesis. Here, we report the identification of a novel subset of monocytes, distinct from TipDCs and lung resident innate populations, that is recruited into the lung during influenza infection in mice. These monocytes had distinct morphology, phenotypic lineage marker expression (CD8α, CD103, F4/80 and Ly6C etc) and transcriptional profile from TipDCs. CCR2 signaling contributed to the recruitment of this monocyte subset into the lung, but it was not indispensable. They were not found in the lung-draining lymph nodes. Functionally, both these monocytes and TipDC could not stimulate CD4 T cell proliferation, but only this subset of monocytes suppressed CD4 and CD8 T cell proliferation, and they also induced high levels of Th17-associated cytokines from CD4 T cells. Our results highlight the heterogeneity of monocyte populations and their functional roles in anti-viral immunity to influenza infection. This heterogeneity may be harnessed for immune modulation strategies as novel therapeutics for influenza infection.