IL‐22 in antifungal immunity

Abstract

Deciphering cellular and molecular mechanisms that maintain host immune homeostasis with fungi and the breakdown of this homeostatic tolerance during fungal infections disease is a challenge in medical mycology. In fact, the virulence of fungi may be determined by the interaction between fungi and the host immune status and its classification as a commensal microorganism or a pathogen may shift depending on the balance. In addition to the central role of the IL-12/IFN-c-dependent Th1 responses in cell-mediated immune protection against fungi, Th17 cells provide protection and inflammation at mucosal surfaces, and Tregs fine-tune immune responses to prevent damage to the host. Recent evidence indicates that IL-22-producing cells, employing primitive antifungal effector mechanisms, contribute to antifungal resistance at mucosal surfaces under conditions of defective adaptive immunity. The fact that IL-22 production is driven by commensals points to the need of an integrated, systems biology approach to improve our understanding of the inherent and intimate mechanisms underlying multilevel host-fungus interactions.

Autoantibodies to IL-17A may be Correlated with the Severity of Mucocutaneous Candidiasis in APECED Patients

“…The other five patients with the same genotype or heterozygous AIRE mutation had low or undetectable anti-IL-17A antibody levels and were asymptomatic or presented only mild and transient signs of mucocutaneous candidiasis. Previous studies have suggested that IL-22 plays an important role in the protection of skin and epithelial surfaces against Candida infection [6,39]. It has been reported that IL-22-producing cells help to protect mucosal surfaces against fungal infection in conditions of defective adaptive immunity, through a primitive antifungal effector mechanism [6,39].…”

“…Previous studies have suggested that IL-22 plays an important role in the protection of skin and epithelial surfaces against Candida infection [6,39]. It has been reported that IL-22-producing cells help to protect mucosal surfaces against fungal infection in conditions of defective adaptive immunity, through a primitive antifungal effector mechanism [6,39]. Furthermore, IL-22 has been reported to play a role in candidiasis, by controlling fungal invasion and epithelial homeostasis [39].…”

“…It has been reported that IL-22-producing cells help to protect mucosal surfaces against fungal infection in conditions of defective adaptive immunity, through a primitive antifungal effector mechanism [6,39]. Furthermore, IL-22 has been reported to play a role in candidiasis, by controlling fungal invasion and epithelial homeostasis [39]. All six patients included in this study had high levels of anti-IL-22 autoantibodies, but only Patient 2, with high levels of anti-IL-17A antibodies, displayed a predisposition to severe CMC.…”

Role of IL-22 in Microbial Host Defense

“…From these reports, it appears that both IL-22 as well as IL-17 are required for full protection against C. albicans infection. The specific role and requirement of each individual cytokine still need further clarification (Zelante et al 2011). …”

Pathogenic NLRP3 Inflammasome Activity during Candida Infection Is Negatively Regulated by IL-22 via Activation of NLRC4 and IL-1Ra

“…IL-22 is known to mediate anticandidal resistance at mucosal surfaces under conditions of defective adaptive immunity (Zelante et al, 2011), an activity to which the local microbiota crucially contributes (Zelante et al, 2013). Sensing of tissue damage via the NLRP3 or NLRP6 increased the ratio of IL-22/ IL-22 binding proteins (IL-22BP) via an IL-18-dependent downregulation of IL-22BP, thereby linking the activity of IL-22 to inflammasome activation (Huber et al, 2012).…”