Long-term cigarette smoking suppresses NLRP3 inflammasome activation in oral mucosal epithelium and attenuates host defense against Candida albicans in a rat model.

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.