Infection-experienced alveolar macrophages sustain airway T cell memory 3555

Description Emerging evidence has suggested that primary infection and/or insult can “train” or “prime” long-term alterations in the transcriptional and epigenetic profiles of innate immune cells, particularly macrophages. Currently, it is unknown whether those “infection-experienced” macrophages can facilitate adaptive immune memory responses after infection resolution. Here, we show that influenza virus infection induces lasting transcriptional and epigenetic changes in lung alveolar macrophages (AMs) compartment following the resolution of primary infection. Further analysis showed that the IL-1b was persistently upregulated in the “infection-experienced” AMs at the memory phase compared to those of AMs from the naïve mice, and the “primed” AMs represent the major source of IL-1b in the infection-experienced lungs. Strikingly, blocking IL-1β or ablating it in myeloid cells during the memory phase led to decreased number of antigen-specific CD8 resident memory T cells (Trm) specifically in the airway but not the lung parenchyma. Consistently, IL-1b blockade caused diminished Trm-mediated protective immunity during heterologous influenza virus re-challenge. Our data suggest that infection-primed innate immune compartment facilitates protective local adaptive immune memory in the respiratory mucosa after the resolution of primary infection. Our findings may inform future vaccine design aiming to induce strong mucosal CD8 T cell immunity against respiratory viral infections. Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)