We previously showed that CCR5 mediates recruitment of NK cells to the kidney after renal ischemia and reperfusion, which in turn induce the production of CCR5 chemokines by tubular epithelial cells. Recruited NK cells stimulate tubular epithelial cells to secrete CXCR2 chemokine through CD137 ligand, resulting in chemotaxis of neutrophils, major effectors for kidney ischemia-reperfusion injury. In this study, we investigated the involvement of CCR5 in host innate immune responses to Candida albicans, an opportunistic pathogen which infects the kidney of immunocompromised patients. CCR5^-/- mice were shown to be highly susceptible to systemic C. albicans infections. A characteristic feature of infected CCR5^-/- kidneys was decrease in levels of IL-23 and GM-CSF in the kidney. IL-23 was secreted from dendritic cells after C. albicans infection and GM-CSF was produced from NK cells in response to IL-23 in wild-type mice. Infusion of GM-CSF into CCR5^-/- mice significantly recovered their ability to clear C. albicans from the kidney, while injection of IL-23 failed to induce production of GM-CSF. Taken together, our results indicated that CCR5^-/- dendritic cells and NK cells have intrinsic defects in their ability to produce cytokines critical in resistance to anti-C. albicans infections.

CITATION INFORMATION: Lee J, Tran V, Kim H, Kwon B, Park K, Cho H. CCR5-Mediated Recruitment of NK Cells to the Kidney Is Critical for Resistance to Candida albicans Infections. Am J Transplant. 2017;17 (suppl 3).

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