B cell-derived acetylcholine controls local inflammation and replication of influenza virus during respiratory tract infections

Abstract

Abstract Acetylcholine (ACh), a well-known neurotransmitter, is produced by the action of choline acetyltransferase (ChAT). Recently, ChAT expression was shown also in leukocytes, however, its function there remains to be more fully explored. Flow cytometry revealed that most ChAT-expressing cells in spleen, lymph nodes, lung, and pleural cavity of ChAT-GFP reporter mice are B cells, with B-1 cells having the highest frequency of ChAT+ cells among them. B cell-specific mb1-Cre ChATflx/flx knockouts (BChat-KO) had apparent normal bone marrow B cell development. Also, serum IgG and IgM levels and spontaneous IgM secretion in the spleen were comparable to wild-type littermate controls. Nonetheless, their spleen B-1 cell numbers were reduced. Intranasal infection of BChat-KO with influenza A/Puerto Rico/8/34 showed significantly smaller increases in IgM-secreting cells in the spleen and mediastinal lymph nodes (medLN) at 7 days post-infection (dpi) compared to controls. Inflammation-induced emigration of CD5+ B-1 cells from the pleural cavity to the medLN, which we showed previously to occur early during influenza infection, appeared exaggerated in the BChat-KO mice, leading to reductions in pleural cavity B-1 cells. Additional alterations to the macrophage and neutrophil composition suggested enhanced pleural inflammation in BChat-KO. This was correlated with reduced control of lung virus replication at 7 dpi. Overall, the data suggest a non-redundant function for B cell-derived ACh in the regulation of pleural inflammation and the control of virus replication following infection with influenza A. The study was supported by a grant from the Chan Zuckerberg Initiative to Colin Reardon and Nicole Baumgarth