The NLRP3 Inflammasome-Independent IL-18 Elevation Induced by Candida Albicans Cell Wall

Abstract

Objective: IL-18 has a significant role in host defense and pathogenesis of many inflammatory diseases. IL-18 production initiates if a particular PRR of innate immune cell binds specific PAMP, including O-linked mannan, a Candida albicans cell wall component. The binding of these PAMPs by TLR4 activates the intracellular signal pathway and activates NFkB to induce the production of pro-IL-18. Pro IL-18 undergoes breakdown to IL-18 active by the most common enzyme, caspase-1. Caspase-1 is the result of NLRP3 inflammasome activation. This study aimed to prove that the Candida albicans cell wall can induce IL-18 production and explore the role of NLRP3 inflammasome in that process. Methods: The Male Wistar rats were injected with 8 mg/kg BW/day and 16 mg/kg BW C. albicans cell wall intraperitoneally on 5 consecutive days in 2 periods with 23 days intervals between periods. Rats were sacrificed 24 h after the end of treatment. Expressions of NLRP3 inflammasome of intraperitoneal macrophages were measured by flow cytometry, and the level of IL-18 in blood plasma was measured with the ELISA technique. Results: IL-18 significantly increased in groups injected with 16 mg/kg BW/day but not those with 8 mg/kg BW/day. The expression of NLRP3 inflammasome was significantly increased in the group injected with 8 mg/kg BW/days C. albicans cell wall but not in the group injected with 16 mg/kg BW/days. Regression analysis showed that the increasing level of IL-18 was dependent on the C albicans cell wall dose but independent of the NLRP3inflamassome expression. The NLRP3-inflammasome expression did not depend on C albicans cell wall dose. Conclusions: C. albicans’ cell wall can increase the IL-18 plasma blood level, and the production of IL-18 is independent of NLRP3-inflammasome activation. HIGHLIGHTS C. albicans cell wall induces IL-18 plasma levels that can cause inflammatory diseases C. albicans cell wall induces NLRP3-inflammasome in small doses but not in high dose The elevation of IL-18 is independent of the expression of NLRP3-inflammasome on the macrophage GRAPHICAL ABSTRACT