Nicotine Impairs Macrophage Control of Mycobacterium tuberculosis.

Nicotine Impairs Macrophage Control of Mycobacterium tuberculosis.

Am J Respir Cell Mol Biol. 2017 Apr 11;:

Authors: Bai X, Stitzel JA, Bai A, Zambrano CA, Phillips M, Marrack P, Chan ED

Abstract
Pure nicotine impairs macrophage killing of Mycobacterium tuberculosis (MTB) but it is not known whether the nicotine component in cigarette smoke (CS) plays a role. Moreover, the mechanisms by which nicotine impairs macrophage immunity against MTB have not been explored. To neutralize the effects of nicotine in CS extract, we utilized a competitive inhibitor to the nicotinic acetylcholine receptor (nAChR) - mecamylamine - as well as macrophages derived from mice with genetic disruption of specific subunits of nAChR. We also determined whether nicotine impaired macrophage autophagy and whether nicotine-exposed T regulatory cells (Tregs) could subvert macrophage anti-MTB immunity. Mecamylamine reduced the CS extract increase in MTB burden by 43%. CS extract increase in MTB was also significantly attenuated in macrophages from mice with genetic disruption of either the α7, β2, or β4 subunit of nAChR. Nicotine inhibited autophagosome formation in MTB-infected THP-1 cells and primary murine alveolar macrophages as well as increased the intracellular MTB burden. Nicotine increased migration of THP-1 cells, consistent with the increased number of macrophages found in the lungs of smokers. Nicotine induced Tregs to produce transforming growth factor-beta. Naïve mouse macrophages co-cultured with nicotine-exposed Tregs had significantly greater number of viable MTB recovered with increased interleukin-10 production and urea production but no difference in secreted nitric oxide as compared to macrophages co-cultured with unexposed Tregs. We conclude that nicotine in CS plays an important role in subterfuging macrophage control of MTB infection.

PMID: 28398760 [PubMed - as supplied by publisher]

from Head and Neck on PubMed via xlomafota13 on Inoreader http://ift.tt/2p503zk


http://ift.tt/2p7wytD