Nanjing Stomatological Hospital & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, Jiangsu Province, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, Jiangsu Province, China.
Nanjing Stomatological Hospital & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, Jiangsu Province, China.
Biomed Pharmacother. 2019 May;113:108597. doi: 10.1016/j.biopha.2019.01.058. Epub 2019 Mar 7.
Cigarette smoke (CS) exposure and Candida albicans (C. albicans) infection are epidemiological risk factors for oral diseases, such as oral leukoplakia (OLK). Smoking-induced inflammation and immune modulation are potentially important mechanisms in the development of diseases, although the biological mechanism of how CS exposure impacts host defenses has not been elucidated. The critical components of host defense, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and IL-1β, are required for normal immune function in order to efficiently control infection. This paper studies the molecular mechanism of the immune-suppressive effect of CS on the oral mucosa of animal models. Rats were exposed to intraoral CS to simulate active human smoking and/or to C. albicans for 3 months or 6 months, and their ability to control the infection of C. albicans was examined. The CS and C. albicans co-exposed rats showed early stage lesions of OLK and were more susceptible to C. albicans than those in the C. albicans-exposed group. CS caused a reduced expression of the NLRP3 inflammasome and diminished the secretion of IL-1β and IL-18 maturing by the NLRP3 inflammasome, which were stimulated by C. albicans. CS and immune suppression appear to be closely interwoven at multiple levels. This is the first animal model of active smoking through the mouth, and these data demonstrate that CS suppresses the protective immune response to C. albicans in rats through the NLRP3 inflammasome.
香烟烟雾（CS）暴露和白色念珠菌（C. albicans）感染是口腔疾病（如口腔白斑病[OLK]）的流行病学危险因素。吸烟引起的炎症和免疫调节是疾病发展的潜在重要机制，尽管 CS 暴露如何影响宿主防御的生物学机制尚未阐明。宿主防御的关键成分，NOD 样受体家族吡喃结构域包含 3（NLRP3）炎性小体和 IL-1β，对于正常的免疫功能是必需的，以便有效地控制感染。本文研究了 CS 对动物模型口腔黏膜免疫抑制作用的分子机制。通过口腔内 CS 暴露来模拟人类主动吸烟，并将大鼠暴露于 CS 和/或白色念珠菌中 3 个月或 6 个月，以检查其控制白色念珠菌感染的能力。CS 和白色念珠菌共同暴露的大鼠表现出 OLK 的早期病变，并且比仅暴露于白色念珠菌的大鼠更容易感染白色念珠菌。CS 导致 NLRP3 炎性小体的表达减少，并抑制了 NLRP3 炎性小体刺激的 IL-1β 和 IL-18 的成熟分泌。CS 和免疫抑制似乎在多个层面上紧密交织。这是第一个通过口腔进行主动吸烟的动物模型，这些数据表明 CS 通过 NLRP3 炎性小体抑制了大鼠对白色念珠菌的保护性免疫反应。
