Aiding and Abetting the Enemy: Nicotine Impairs the Macrophage Defense against Mtb.
Aiding and Abetting the Enemy: Nicotine Impairs the Macrophage Defense against Mtb.
复制标题
帮助和教唆敌人：尼古丁损害巨噬细胞对结核分枝杆菌的防御。
DOI：
10.1165/rcmb.2017-0149ed
复制
发表时间：
2017
影响因子：
6.4
通讯作者：
Jeyaseelan,Samithamby
中科院分区：
文献类型：
--
作者：
Kulkarni,Ritwij;Jeyaseelan,Samithamby
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that kills a large number of people in the world (1). In 2015, z10 million new cases of TB and 2 million TB-related deaths were reported globally, earning it a place among the top 10 causes of global mortality (2). The emergence of multidrugresistant TB is a menacing problem (2). An extensive geographical overlap exists between the areas where cigarette smoking is widespread and TB is highly prevalent. In addition, an association between cigarette smoke (CS) exposure and an increased risk of TB in children and adults has been found (3). Cigarette smoking has been shown to double the risk for the disease to develop again in individuals who have been cured of TB, an event termed “recurrent TB”(4). Thus, understanding the fundamental mechanisms by which CS exposure may suppress the host defense against Mtb is critical and timely as we seek to identify improved treatment and prevention strategies.The first line of defense in eliminating Mtb in the lung is mediated by macrophages. Macrophages enter the site of infection, engulf Mtb, and may successfully eliminate it (5). However, Mtb has evolved numerous adaptive strategies for survival within macrophages. These include the abilities to inhibit phagosomelysosome fusion, and to escape from the phagosome and enter the cytoplasm (5). Murine studies have shown that recruitment of significantly fewer immune cells (macrophages, dendritic cells, and T cells) in the lungs of CS-exposed mice may be responsible for an increased pulmonary Mtb burden (6, 7). In addition, CS exposure attenuates cytokine production and Mtb killing by macrophages (8, 9). Up to now, however, no studies have examined molecular mechanisms such as autophagy and the activation of immunosuppressive regulatory T (Treg) cells in the context of nicotine exposure, which suppresses anti-Mtb immunity and thereby allows CS to function as a major immunomodulator. In this issue of the Journal, Bai and colleagues (pp. 324–333) demonstrate that exposure to nicotine impairs the macrophage anti-Mtb defense by regulating two distinct mechanisms: first, it inhibits autophagy; second, it activates immunosuppressive Treg cells (10). Additionally, they found that the suppression of macrophage anti-Mtb immunity is dependent on the binding of nicotine to the nicotinic acetylcholine receptor (nAChR). Autophagy was originally defined as a process by which cellular organelles and proteins sequestered inside a double-membrane vesicle, the autophagosome, are delivered for lysosomal degradation (11). Autophagy is known to represent a crucial anti-Mtb mechanism of the macrophage, and the ability to suppress autophagy is linked to Mtb virulence (11). Nevertheless, the effects of impairment of autophagy by CS exposure on virulence in macrophages infected with Mtb have not been explored. Bai and colleagues (10) demonstrate that in a human myelomonocytic cell line (THP-1), Mtb-induced LC3II expression (a marker of autophagic activation) was significantly reduced by pretreatment with nicotine in a dose-dependent manner. Similarly, when compared with the medium-exposed controls,
