Disseminated Candida albicans infection is potentially fatal and frequently causes acute kidney injury. A recent study by Partha Biswas and colleagues provides new insights into the role of renal tubular epithelial cells (RTECs) in the defence against this fungal pathogen.

“We previously showed that IL-17 has a kidney-protective role during disseminated candidiasis,” says Biswas. “However, there is controversy regarding the cellular source of IL-17 and the contribution of IL-17-responsive renal cells to immunity against C. albicans. Understanding these issues could lead to improvements in immune-based therapies for this poorly understood infection.”

The researchers now report that TCRγδ+ T cells are the primary source of IL-17 in C. albicans-infected kidneys. Using chimeric mice, they demonstrate that IL-17 receptor A (IL-17RA) expression on haematopoietic cells is not required for immunity to systemic C. albicans infection. However, infected mice with specific knockout of IL-17RA in RTECs (Il17ra∆RTEC) showed more severe renal damage and reduced survival compared with wild-type controls. Their increased susceptibility to C. albicans infection was very similar to that of Il17ra-knockout mice, suggesting a key role of IL-17RA signalling in RTECs in the defence against this pathogen.

The researchers also show increased apoptosis and reduced activation of the kallikrein–kinin system (KKS) in RTECs in response to C. albicans infection in Il17ra∆RTEC mice compared with wild-type controls. Consistent with these findings, treatment with bradykinin — the end product of the KKS — significantly increased the survival of the infected Il17ra∆RTEC mice.

“During systemic infection with C. albicans, IL-17 activity within the kidney is remarkably restricted to non-haematopoietic cells,” concludes Biswas. “IL-17 is produced by TCRγδ+ T cells and activates the KKS in RTECs, which is essential to limit apoptosis of renal cells and prevent kidney damage during fungal invasion. These findings may lead to the use of targeted therapies that impact the bradykinin pathway to counter renal damage during disseminated candidiasis.”