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  • 제20권6호
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  • Pages.49.1-49.15
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  • 2020
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  • 1598-2629(pISSN)
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  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
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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 (BK21 Integrated Immunometabolism Education and Research Team, School of Biological Sciences, University of Ulsan) ;
  • Vuvi G. Tran (BK21 Integrated Immunometabolism Education and Research Team, School of Biological Sciences, University of Ulsan) ;
  • Saerom Lee (Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan) ;
  • Minji Kim (Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan) ;
  • Sang W. Kang (Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan) ;
  • Juyang Kim (Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan) ;
  • Hye J. Kim (Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan) ;
  • Jong S. Lee (Division of Nephrology, Department of Internal Medicine, Ulsan University Hospital, School of Medicine, University of Ulsan) ;
  • Hong R. Cho (Biomedical Research Center, Ulsan University Hospital, School of Medicine, University of Ulsan) ;
  • Byungsuk Kwon (BK21 Integrated Immunometabolism Education and Research Team, School of Biological Sciences, University of Ulsan)
  • 투고 : 2020.08.19
  • 심사 : 2020.11.12
  • 발행 : 2020.12.31
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초록

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.

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과제정보

This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean government (NRF-2020M33A9D303789111 and NRF-2019R1A105584412).

참고문헌

  1. Kullberg BJ, Arendrup MC. Invasive candidiasis. N Engl J Med 2015;373:1445-1456. https://doi.org/10.1056/NEJMra1315399
  2. Romani L. Immunity to fungal infections. Nat Rev Immunol 2011;11:275-288. https://doi.org/10.1038/nri2939
  3. Netea MG, Joosten LA, van der Meer JW, Kullberg BJ, van de Veerdonk FL. Immune defence against Candida fungal infections. Nat Rev Immunol 2015;15:630-642. https://doi.org/10.1038/nri3897
  4. Lionakis MS. Genetic susceptibility to fungal infections in humans. Curr Fungal Infect Rep 2012;6:11-22. https://doi.org/10.1007/s12281-011-0076-4
  5. Leroy O, Gangneux JP, Montravers P, Mira JP, Gouin F, Sollet JP, Carlet J, Reynes J, Rosenheim M, Regnier B, et al. Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005-2006). Crit Care Med 2009;37:1612-1618. https://doi.org/10.1097/CCM.0b013e31819efac0
  6. Lionakis MS, Lim JK, Lee CC, Murphy PM. Organ-specific innate immune responses in a mouse model of invasive candidiasis. J Innate Immun 2011;3:180-199. https://doi.org/10.1159/000321157
  7. Geijtenbeek TB, Gringhuis SI. C-type lectin receptors in the control of T helper cell differentiation. Nat Rev Immunol 2016;16:433-448.
  8. Brown GD, Willment JA, Whitehead L. C-type lectins in immunity and homeostasis. Nat Rev Immunol 2018;18:374-389.
  9. Legrand F, Lecuit M, Dupont B, Bellaton E, Huerre M, Rohrlich PS, Lortholary O. Adjuvant corticosteroid therapy for chronic disseminated candidiasis. Clin Infect Dis 2008;46:696-702. https://doi.org/10.1086/527390
  10. Majer O, Bourgeois C, Zwolanek F, Lassnig C, Kerjaschki D, Mack M, Muller M, Kuchler K. Type I interferons promote fatal immunopathology by regulating inflammatory monocytes and neutrophils during Candida infections. PLoS Pathog 2012;8:e1002811.
  11. Bar E, Whitney PG, Moor K, Reis e Sousa C, LeibundGut-Landmann S. IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells. Immunity 2014;40:117-127. https://doi.org/10.1016/j.immuni.2013.12.002
  12. Whiteney PG, Bar E, Osorio F, Rogers NC, Schraml BU, Deddouche S, LeibundGut-Landmann S, Reis e Sousa C. Syk signaling in dendritic cells orchestrates innate resistance to systemic fungal infection. PLoS Pathog 2014;10:e1004276.
  13. Dominguez-Andres J, Feo-Lucas L, Minguito de la Escalera M, Gonzalez L, Lopez-Bravo M, Ardavin C. Inflammatory Ly6Chigh monocytes protect against candidiasis through IL-15-driven NK cell/neutrophil activation. Immunity 2017;46:1059-1072.e4. https://doi.org/10.1016/j.immuni.2017.05.009
  14. Ngo LY, Kasahara S, Kumasaka DK, Knoblaugh SE, Jhingran A, Hohl TM. Inflammatory monocytes mediate early and organ-specific innate defense during systemic candidiasis. J Infect Dis 2014;209:109-119. https://doi.org/10.1093/infdis/jit413
  15. Kim HJ, Lee JS, Kim A, Koo S, Cha HJ, Han JA, Do Y, Kim KM, Kwon BS, Mittler RS, et al. TLR2 signaling in tubular epithelial cells regulates NK cell recruitment in kidney ischemia-reperfusion injury. J Immunol 2013;191:2657-2664.
  16. Khan IA, Thomas SY, Moretto MM, Lee FS, Islam SA, Combe C, Schwartzman JD, Luster AD. CCR5 is essential for NK cell trafficking and host survival following Toxoplasma gondii infection. PLoS Pathog 2006;2:e49.
  17. Borregaard N, Cowland JB. Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 1997;89:3503-3521. https://doi.org/10.1182/blood.V89.10.3503
  18. Lionakis MS, Levitz SM. Host control of fungal infections: lessen from basic studies and human cohorts. Annu Rev Immunol 2018;36:157-191. https://doi.org/10.1146/annurev-immunol-042617-053318
  19. Le HT, Tran VG, Kim W, Kim J, Cho HR, Kwon B. IL-33 priming regulates multiple steps of the neutrophil-mediated anti-Candida albicans response by modulating TLR and dectin-1 signals. J Immunol 2012;189:287-295.
  20. Kim HJ, Lee JS, Kim JD, Cha HJ, Kim A, Lee SK, Lee SC, Kwon BS, Mittler RS, Cho HR, et al. Reverse signaling through the costimulatory ligand CD137L in epithelial cells is essential for natural killer cellmediated acute tissue inflammation. Proc Natl Acad Sci U S A 2012;109:E13-E22.
  21. Zhang ZX, Shek K, Wang S, Huang X, Lau A, Yin Z, Sun H, Liu W, Garcia B, Rittling S, et al. Osteopontin expressed in tubular epithelial cells regulates NK cell-mediated kidney ischemia reperfusion injury. J Immunol 2010;185:967-973.
  22. Li SS, Kyei SK, Timm-McCann M, Ogbomo H, Jones GJ, Shi M, Xiang RF, Oykhman P, Huston SM, Islam A, et al. The NK receptor NKp30 mediates direct fungal recognition and killing and is diminished in NK cells from HIV-infected patients. Cell Host Microbe 2013;14:387-397. https://doi.org/10.1016/j.chom.2013.09.007
  23. Li SS, Ogbomo H, Mansour MK, Xiang RF, Szabo L, Munro F, Mukherjee P, Mariuzza RA, Amrein M, Vyas JM, et al. Identification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida. Nat Commun 2018;9:751. 
  24. Voigt J, Hunniger K, Bouzani M, Jacobsen ID, Barz D, Hube B, Loffler J, Kurzai O. Human natural killer cells acting as phagocytes against Candida albicans and mounting an inflammatory response that modulates neutrophil antifungal activity. J Infect Dis 2014;209:616-626. https://doi.org/10.1093/infdis/jit574
  25. Lionakis MS, Fischer BG, Lim JK, Swamydas M, Wan W, Lee CC, Cohen JI, Scheinberg P, Gao JL, Murphy PM. Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis. PLoS Pathog 2012;8:e1002865.
  26. Lionakis MS, Swamydas M, Fischer BG, Plantinga TS, Johnson MD, Jaeger M, Green NM, Masedunskas A, Weigert R, Mikelis C, et al. CX3CR1-dependent renal macrophage survival promotes Candida control and host survival. J Clin Invest 2013;123:5035-5051. https://doi.org/10.1172/JCI71307
  27. Swamydas M, Gao JL, Break TJ, Johnson MD, Jaeger M, Rodriguez CA, Lim JK, Green NM, Collar AL, Fischer BG, et al. CXCR1-mediated neutrophil degranulation and fungal killing promote Candida clearance and host survival. Sci Transl Med 2016;8:322ra10.
  28. Swamydas M, O'Hayre M, Sajib MS, Hoffman KW, Singh SP, Mourad A, Johnson MD, Ferre EM, Farber JM, Lim JK, et al. The homozygous CXCR1-M280 mutation impairs human monocyte survival. JCI Insight 2018;3:e95417.
  29. Codarri L, Gyulveszi G, Tosevski V, Hesske L, Fontana A, Magnenat L, Suter T, Becher B. RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 2011;12:560-567. https://doi.org/10.1038/ni.2027
  30. El-Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F, Zhang GX, Dittel BN, Rostami A. The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GMCSF. Nat Immunol 2011;12:568-575. https://doi.org/10.1038/ni.2031
  31. Dougan M, Dranoff G, Dougan SK. IL-2, and IL-5 family of cytokines: regulators of inflammation. Immunity 2019;50:796-811. https://doi.org/10.1016/j.immuni.2019.03.022
  32. Pearson C, Thornton EE, McKenzie B, Schaupp AL, Huskens N, Griseri T, West N, Tung S, Seddon BP, Uhlig HH, et al. ILC3 GM-CSF production and mobilisation orchestrate acute intestinal inflammation. eLife 2016;5:e10066.
  33. Hirota K, Hashimoto M, Ito Y, Matsuura M, Ito H, Tanaka M, Watanabe H, Kondoh G, Tanaka A, Yasuda K, et al. Autoimmune Th17 cells induced synovial stromal and innate lymphoid cell secretion of the cytokine GM-CSF to initiate and augment autoimmune arthritis. Immunity 2018;48:1220-1232.e5. https://doi.org/10.1016/j.immuni.2018.04.009