B cells regulate early lung macrophage activation during influenza virus infection via production of acetylcholine

Abstract The neurotransmitter Acetylcholine (ACh) is produced by the enzyme choline acetyltransferase (ChAT). Recently, ChAT expression was found in leukocytes, however, function of leukocyte-derived ACh incompletely understood. Flow cytometry showed that most ChAT-expressing cells spleen, lymph nodes, lung, and pleural cavity ChAT-GFP reporter mice are B cells. B-1 contain highest frequencies ChAT-expressors. cell-specific Mb1-Cre+ fl/flknockouts (B Chat-KO) comparable bone marrow cell development steady-state serum IgG IgM production as wild-type littermate controls. Given earlier studies showing TLR-mediated induction cells, we studied infection with Influenza A/Puerto Rico/8/34. Infection resulted an accumulation lungs 1- 3-days post (dpi). Moreover, Chat-KOmice significant reductions viral loads at 1 dpi, suggesting cell-derived regulates early innate antiviral immunity. Indeed, Chat-KOshowed increased TNFa-expressing CD86 hilung macrophages 1dpi. Consistent this, acetylcholine reduced TNFa-expression LPS-stimulated vitro. In contrast, Lck-Cre+ fl/flthat lack T no difference lung 1dpi compared to controls, numbers draining nodes did not increase until 7dpi. Together these data suggest a new regulatory for virus-induced inflammation via ACh. - Chan Zuckerberg Initiative Colin Reardon Nicole Baumgarth NIH/NIAID R01AI148652