Defective IL-17- and IL-22-dependent mucosal host response to Candida

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213580/?report=classic

Treatment of infected Tg mice with the combination of IL-17 and Il-22 by the intraperitoneal route every 2 days for 14 days significantly reduced oral burdens of C. albicans, markedly decreased the density of C. albicans on histopathology of the oral epithelium, and restored the expression of S100a8 and Ccl20.

The cytokine dosage of 3 μg was selected because it is at the upper end of the range of dosages (0.5-3 μg) previously administered to mice by the intraperitoneal route without undesirable effects [72-75]. Because this combined cytokine treatment did not fully reduce oral burdens of C. albicans to levels in the non-Tg mice, we cannot exclude the possibility that a further reduction may be achievable with daily treatment, or by increasing the cytokine dosage to the maximum tolerated dose, to be determined by dose-ranging studies.

Alternately, the defects of mucosal immunity which cause susceptibility to OPC herbal cancer cure in the Tg mice could partially involve Th1 effector mechanisms [51] which are IL-17- and IL-22-independent. The requirement for combined treatment with both IL-17 and IL-22 to restore mucosal immunity to C. albicans extends in vitro studies which showed that IL-22 in conjunction with IL-17 additively enhance the expression of S100A8 by keratinocytes [15]. The mechanism of this cooperation between IL-17 and IL-22 for induction of antimicrobial peptides is unknown but may be the result of convergence of the STAT3 and NF-κB pathways [18]. Although studies in IL-22KO and IL-17RAKO mice have shown that IL-22 has a significant but lesser protective role than IL-17 in OPC herbal cancer cure [11], the present results demonstrate that neither cytokine is dispensable for protection against OPC herbal cancer cure in the context of HIV transgene expression.

This paradigm is likely applicable to other susceptible hosts, such as patients with chronic mucocutaneous candidiasis who exhibit reduced production of IL-17 and IL-22 [76].