J IMMUNOL：空气污染与结核易感性间的可能联系

据研究，在常见城市空气污染与重要免疫细胞功能改变之间，可能存在一种相关性，其中免疫细胞是能防御结核分支杆菌（Mycobacterium tuberculosis）的细胞。在流行病学方面，已有证据证明结核病与吸烟及某些室内空气污染有关系，将这种关系类比于室外空气污染看起来是合乎逻辑的。

据估计，全世界约有800-1000万人受结核病折磨，每年造成150万人死亡。在低收入和中等收入国家，结核病发病率尤其高，因此这些国家正处于工业快速增长和城市交通机动车辆大幅增加阶段，空气污染将日趋严重。

最近，一项研究发表在期刊Journal of Immunology上，它指出：接触柴油机废气颗粒（DEP）可抑制巨噬细胞功能（一种白细胞，能摄取异物、细菌），使接触它的人抗新结核分支杆菌感染的能力更低下。该研究以汽车柴油引擎产生的DEP作为空气污染微粒，对20个健康人血样进行研究，结果显示：接触DEP使细胞敏感性低下，对引发结核的细菌刺激脱敏，如果细胞先接触DEP，这种效应则远远大于那些同时接触DEP 与结核分枝杆菌的细胞。此研究所用的污染模型可能就是实际情况，接下来要做的就是通过更大型的流行病学研究来确证这些研究结果，在实际环境中开展该研究。（生物谷bioon.com）

doi:10.4049/jimmunol.1101380
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Suppression of the NF- B Pathway by Diesel Exhaust Particles Impairs Human Antimycobacterial Immunity

S. Sarkar, Y. Song, S. Sarkar, H. M. Kipen, R. J. Laumbach, J. Zhang, P. A. Ohman Strickland, C. R. Gardner, S. Schwander

Epidemiological studies suggest that chronic exposure to air pollution increases susceptibility to respiratory infections, including tuberculosis in humans. A possible link between particulate air pollutant exposure and antimycobacterial immunity has not been explored in human primary immune cells. We hypothesized that exposure to diesel exhaust particles (DEP), a major component of urban fine particulate matter, suppresses antimycobacterial human immune effector cell functions by modulating TLR-signaling pathways and NF-κB activation. We show that DEP and H37Ra, an avirulent laboratory strain of Mycobacterium tuberculosis, were both taken up by the same peripheral human blood monocytes. To examine the effects of DEP on M. tuberculosis-induced production of cytokines, PBMC were stimulated with DEP and M. tuberculosis or purified protein derivative. The production of M. tuberculosis and purified protein derivative-induced IFN-γ, TNF-α, IL-1β, and IL-6 was reduced in a DEP dose-dependent manner. In contrast, the production of anti-inflammatory IL-10 remained unchanged. Furthermore, DEP stimulation prior to M. tuberculosis infection altered the expression of TLR3, -4, -7, and -10 mRNAs and of a subset of M. tuberculosis-induced host genes including inhibition of expression of many NF-κB (e.g., CSF3, IFNG, IFNA, IFNB, IL1A, IL6, and NFKBIA) and IFN regulatory factor (e.g., IFNG, IFNA1, IFNB1, and CXCL10) pathway target genes. We propose that DEP downregulate M. tuberculosis-induced host gene expression via MyD88-dependent (IL6, IL1A, and PTGS2) as well as MyD88-independent (IFNA, IFNB) pathways. Prestimulation of PBMC with DEP suppressed the expression of proinflammatory mediators upon M. tuberculosis infection, inducing a hyporesponsive cellular state. Therefore, DEP alters crucial components of antimycobacterial host immune responses, providing a possible mechanism by which air pollutants alter antimicrobial immunity.