Nicotine modulates molecules of the innate immune response in epithelial cells and macrophages during infection with M. tuberculosis

Abstract

Summary Smoking increases susceptibility to becoming infected with and developing tuberculosis. Among the components of cigarette smoke, nicotine has been identified as the main immunomodulatory molecule; however, its effect on the innate immune system is unknown. In the present study, the effect of nicotine on molecules of the innate immune system was evaluated. Lung epithelial cells and macrophages were infected with Mycobacterium tuberculosis (Mtb) and/or treated with nicotine. The results show that nicotine alone decreases the expression of the Toll-like receptors (TLR)-2, TLR-4 and NOD-2 in all three cell types, as well as the production of the SP-D surfactant protein in type II pneumocytes. Moreover, it was observed that nicotine decreases the production of interleukin (IL)-6 and C-C chemokine ligand (CCL)5 during Mtb infection in epithelial cells (EpCs), whereas in macrophages derived from human monocytes (MDMs) there is a decrease in IL-8, IL-6, tumor necrosis factor (TNF)-α, IL-10, CCL2, C-X-C chemokine ligand (CXCL)9 and CXCL10 only during infection with Mtb. Although modulation of the expression of cytokines and chemokines appears to be partially mediated by the nicotinic acetylcholine receptor α7, blocking this receptor found no effect on the expression of receptors and SP-D. In summary, it was found that nicotine modulates the expression of innate immunity molecules necessary for the defense against tuberculosis.

Nicotine Modulates MyD88-Dependent Signaling Pathway in Macrophages during Mycobacterial Infection

“…However, in MAP-infected macrophages, nicotine has significantly decreased expression of both TLR2 and TLR4 . Although similar observations were reported in MTB-infected macrophages derived monocyte (MDMs) and in lung epithelial cells [ 34 , 38 ], this is the first data to show a negative effect for nicotine on TLR2 expression in macrophages infected with MAP. We are still uncertain about the impact of this observation on MAP viability and burden in macrophages.…”

“…Recent reports suggested the involvement of TLR2 in MTB infection especially with cell wall derivatives [ 33 , 34 ]. Other study showed that TLR2-deficient mice failed to develop immune response against MTB [ 35 ].…”

“…However, TLR4 -deficient mice were active and responded properly during MTB infection [ 36 ]. In Gram-negative bacterial infection and due to LPS molecules, TLR4 was reported to play a role in recognition of enteric pathogens [ 34 ]. In this study, we investigated the interaction of MAP, a CD-associated pathogen, with both TLR2 and TLR4 .…”

The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis

“…ACh has not been studied in a pulmonary TB context. However, several studies have demonstrated that nicotine, a major constituent of cigarette smoke, worsens disease outcomes through nAChR stimulation ( 15 – 17 ). Additionally, receptors involved in the PPIR are implicated in the pathogenesis of active TB ( 18 , 19 ).…”

The first results nicotine dependence treatment by varenicline in patients with tuberculosis

“…Это происходит как в результате непосредственного токсического воздействия компонентов табачного дыма на клетки бронхов и легкого, иммунной системы, так и влияя на фармакокинетику противотуберкулезных препаратов [3]. Кроме того, исследования влияния никотина на эпителиальные клетки легких и макрофагов, инфицированных Mycobacterium tuberculosis, показали, что никотин снижает экспрессию Toll-подобных рецепторов TLR-2, TLR-4 и NOD-2 в клетках, а также продуцирование белка сурфактанта SP-D в пневмоцитах типа II, уменьшает выработку интерлейкина (IL-6) [4].…”