B cells control lung interstitial macrophage-mediated inflammation and innate defenses after influenza infection via production of acetylcholine

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B126
Abstract ID: 4380

Presenting Author:
Antonio Cembellin-Prieto , Graduate Student Researcher at Univ. of California, Davis, Johns Hopkins Bloomberg Sch. of Pub. Hlth.

Abstract:

Innate immune defenses are vital for rapid control of acute respiratory infections, but they need to be regulated to avoid tissue damage. Using reporter mice in which cells that can produce the metabolite and neurotransmitter, acetylcholine (ACh), are marked by choline acetyltransferase (ChAT)-GFP, we found that >90% of GFP+ leukocytes are B cells. This included B cells in the respiratory tract, with the highest frequencies of ChAT+ cells found among innate-like B-1 cells, both prior to and within a few days post infection (dpi) with influenza A/Puerto Rico/8/34. In contrast, ChAT-expressing T cells appeared in the lungs not until around 7 dpi. Deletion of ChAT in B but not T cells significantly increased frequencies of activated lung interstitial macrophages (IM) able to produce TNFa at 1 dpi, correlating with increased lung pathology but also significant reductions in lung viral loads. Conversely, TNFa blockade via mAb treatment increased viral loads at that time. Consistent with a crosstalk between IM and ChAT+ B cells, a7 nicotinic ACh receptor KO mice showed increased IM activation and TNFa expression at 1 dpi and ACh suppressed TNFa production by LPS-stimulated IM in vitro. Together the study identifies a novel regulatory role for early-activated ACh-producing B cells in controlling IM-mediated lung inflammation following influenza virus infection.