CCR5-Mediated Recruitment of NK Cells to the Kidney is a Critical Step for Host Defense to Candida albicans Infection
1Department of Surgery, Ulsan University Hospital, Ulsan, Korea, Republic of, 2School of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea, Ulsan, Korea, Republic of, 31School of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea, Ulsan, Korea, Republic of, 4Biomedical Research Center, Ulsan University Hospital, Ulsan, Korea, Republic of, 5Division of Nephrology, Department of Internal Medicine, Ulsan University Hospital, Ulsan, Korea, Republic of, 6Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan, Ulsan, Korea, Republic of
Meeting: 2019 American Transplant Congress
Abstract number: A341
Keywords: Fungal infection, Immunosuppression, Mice, knockout, Natural killer cells
Session Information
Session Name: Poster Session A: Transplant Infectious Diseases
Session Type: Poster Session
Date: Saturday, June 1, 2019
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: Candida albicans infection causes a high rate of mortality in immunocompromised or transplant patients. In this study, we investigated the role of CCR5 that regulates the trafficking of various immune cells to the site of infection.
*Methods: 2 x 105 CFUs of Candida albicans were intravenously infection in wild-type and CCR5-/- mice. Survival rate, kidney injury, fungal counting, and characteristics of renal inflammation was analysis using conventional immunological techniques. In vitro culture of dendritic cells (DCs) and monocytes was performed to their ability to produce IL-23 and IL-15 in response to GM-CSF plus heat-killed C. albicans.
*Results: Expression of CCR5 and its ligands were rapidly increased in the kidney after systemic C. albicans infection and infected CCR5-/- mice showed 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. ablicans infection was due to their impaired capacity of 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 rapidly induced expression of IL-23 and IL-15 by CD11b+CD11c+ DCs and Ly6C+ monocytes, respectively. IL-23 and IL-15 in turn augmented the fungicidal activity of neutrophils through GM-CSF production by NK cells. As GM-CSF potentiated production of IL-23 and IL-15 in response to C. albicans, a positive feedback loop formed between NK cells and DCs or Ly6C+ monocytes seemed to function as a central amplification point for host defense.
*Conclusions: Taken together, our results suggest that CCR5-mediated recruitment of NK cells to the site of fungal replication is a critical step that underlies innate resistance to systemic C. albicans infection.
To cite this abstract in AMA style:
Cho HR, Tran VG, Nguyen NN, Lee S, Kang SW, Kim J, Kim HJ, Park SJ, Lee JS, Kwon B. CCR5-Mediated Recruitment of NK Cells to the Kidney is a Critical Step for Host Defense to Candida albicans Infection [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/ccr5-mediated-recruitment-of-nk-cells-to-the-kidney-is-a-critical-step-for-host-defense-to-candida-albicans-infection/. Accessed May 9, 2025.« Back to 2019 American Transplant Congress