CCR5-mediated Recruitment of NK Cells to the Kidney Is a Critical Step for Host Defense to Systemic Candida albicans Infection

Nu Z N Nguyen; Vuvi G Tran; Saerom Lee; Minji Kim; Sang W Kang; Juyang Kim; Hye J Kim; Jong S Lee; Hong R Cho; Byungsuk Kwon

doi:10.4110/in.2020.20.e49

CCR5-mediated Recruitment of NK Cells to the Kidney Is a Critical Step for Host Defense to Systemic Candida albicans Infection

Immune Netw. 2020 Dec 14;20(6):e49. doi: 10.4110/in.2020.20.e49. eCollection 2020 Dec.

Authors

Nu Z N Nguyen¹, Vuvi G Tran¹, Saerom Lee², Minji Kim², Sang W Kang², Juyang Kim², Hye J Kim², Jong S Lee³, Hong R Cho^{2

4}, Byungsuk Kwon^{1

2}

Affiliations

¹ BK21 Integrated Immunometabolism Education and Research Team, School of Biological Sciences, University of Ulsan, Ulsan 44610, Korea.
² Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea.
³ Division of Nephrology, Department of Internal Medicine, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea.
⁴ Department of Surgery, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea.

Abstract

C-C chemokine receptor type 5 (CCR5) regulates the trafficking of various immune cells to sites of infection. In this study, we showed that expression of CCR5 and its ligands was rapidly increased in the kidney after systemic Candida albicans infection, and infected CCR5^-/- mice exhibited increased mortality and morbidity, indicating that CCR5 contributes to an effective defense mechanism against systemic C. albicans infection. The susceptibility of CCR5^-/- mice to C. albicans infection was due to impaired fungal clearance, which in turn resulted in exacerbated renal inflammation and damage. CCR5-mediated recruitment of NK cells to the kidney in response to C. albicans infection was necessary for the anti-microbial activity of neutrophils, the main fungicidal effector cells. Mechanistically, C. albicans induced expression of IL-23 by CD11c⁺ dendritic cells (DCs). IL-23 in turn augmented the fungicidal activity of neutrophils through GM-CSF production by NK cells. As GM-CSF potentiated production of IL-23 in response to C. albicans, a positive feedback loop formed between NK cells and DCs seemed to function as an amplification point for host defense. Taken together, our results suggest that CCR5-mediated recruitment of NK cells to the site of fungal infection is an important step that underlies innate resistance to systemic C. albicans infection.

Keywords: CCR5; Candida albicans; Dendritic cells; GM-CSF; IL-23; NK cells.