Patients with Chronic Mucocutaneous Candidiasis Exhibit Reduced Production of Th17-Associated Cytokines IL-17 and IL-22

Abstract

Chronic mucocutaneous candidiasis (CMC) constitutes a selective inability to clear infection with the yeast Candida, resulting in persistent debilitating inflammation of skin, nails, and mucous membranes. The underlying defect is unknown. Only recently, IL-17-producing T cells have been reported to be involved in clearing Candida infections. In order to characterize T cellular immune response to Candida, we analyzed T-cell cytokine secretion to Candida antigen and mitogenic stimuli in CMC patients, immunocompetent patients suffering from acute Candida infection, and healthy volunteers. Peripheral blood mononuclear cells (PBMCs) from CMC patients produced significantly lower amounts of IL-17 and IL-22 mRNA and protein when stimulated with Candida albicans or mitogen in vitro compared with that in matched healthy individuals. Additionally, PBMCs from immunocompetent Candida-infected patients secreted more IL-17 and IL-22 than those of both CMC patients and healthy, non-infected controls. Flow cytometry revealed a decreased number of CCR6+ IL-17-producing T cells in CMC patients, whereas the amount of CCR6+/CCR4+ cells was not altered. Levels of differentiating cytokines for human Th17 cells, IL-1beta and IL-6, tended to be higher in CMC patients. The inability to clear C. albicans in CMC patients could be due to a defect in the immune response of IL-17-producing T cells.

Baofukang suppository promotes the repair of vaginal epithelial cells in response to candida albicans

“…An impaired IL-17 response appears to be responsible for the pathogenesis of chronic mucocutaneous candidiasis (Eyerich et al 2008). Our data also affirm that the Baofukang suppository partly restores IL-17-production by VECs against Candida infection in vitro, thus, initiating an early Th17-type innate immune response against extracellular Candida adhesion and filamentation.…”

“…Moreover, evidence has been mounting that a Th17-driven immune response plays a predominant role in modulating a defensive mucosal immune response against Candida in both mice and humans (Huang et al 2004;Conti et al 2009;Eyerich et al 2008). An impaired IL-17 response appears to be responsible for the pathogenesis of chronic mucocutaneous candidiasis (Eyerich et al 2008).…”

Dendritic cell interactions withHistoplasmaandParacoccidioides

“…65 Th17 cells also have an increasingly recognized role in the adaptive immune response to a variety of fungal pathogens. 66,67 Chamilos et al found that exposure of the b-glucan component of the cell wall of a mutant strain of H. capsulatum decreased its pathogenicity and stimulated an increased production of IL-23 by DCs and a resultant Th17 antifungal response. 68 This was found using a mutant strain of H. capsulatum that is unable to generate a-glucan, thereby exposing b-glucan to DCs.…”

Memory IL‐22‐producing CD4+ T cells specific for Candida albicans are present in humans

“…Two recent studies have highlighted a new role for IL-22 in mediating protection against bacterial infections in a mouse model [11,12], leading to the question of whether IL-22 had an effect on protection against fungal infection. Recent reports indicated that a disease with chronic candidiasis (CMC and HIES) exhibited a deficiency for IL-22 and IL-17 [13,14]. Based on the increased expression of IL-22R1 in the skin and mucous membranes and the anti-fungal effect of hBD induced by IL-22, it was suggested that IL-22 may also play a critical role in fungal infections.…”