Invariant natural killer T (iNKT) cell deficiency in chronic mucocutaneous candidiasis--a consequence or a cause?

Chronic mucocutaneous candidiasis (CMC) is a group of heterogeneous disorders characterised by primary selective susceptibility to chronic, recurrent Candida infections. The genetic defect of one subgroup of CMC patients have been identified as mutations of the autoimmune regulator (AIRE) gene. Recent data implicated the AIRE gene in iNKT cell development, raising the possibility that iNKT cells may be important in defending against Candida infections. In this study, we enumerated the circulating iNKT frequency in 22 CMC patients (9 with AIRE gene mutations) and 25 healthy controls. We also examined the effect of Candida stimulation on iNKT cells in vitro. Our data demonstrated that peripheral iNKT cell frequency is significantly reduced in CMC patients compared to healthy controls, regardless of their AIRE gene mutation status. Direct stimulation with heat-inactivated whole Candida did not induce iNKT cell proliferation. Furthermore, circulating iNKT cell frequencies in some healthy controls were comparable to CMC patients. These observations suggest that iNKT cell deficiency is part of the CMC disease phenotype irrespective of the presence of AIRE gene mutations but does not appear to confer susceptibility to chronic Candida infections. We postulate that the reduced circulating iNKT cell frequency in CMC is a consequence rather than a cause of chronic Candida infections.