title: The NK receptor NKp30 mediates direct fungal recognition and killing and is diminished in NK cells from HIV-infected patients.
abstract: Natural killer (NK) cells are a subset of immune effectors that directly bind and kill fungi via a perforin-dependent mechanism. The receptor mediating this activity and its potential role in disease remain unknown. Using an unbiased approach, we determined that NKp30 is responsible for recognition and killing of the fungal pathogens Cryptococcus and Candida. NKp30 was required for NK cell-fungal conjugate formation, phosphatidylinositol 3-kinase (PI3K) signaling, and perforin release. Because fungal infections are a leading cause of death in AIDS patients, we examined NKp30 expression in HIV-infected patients. NK cells from these patients had diminished NKp30 expression, defective perforin release, and blunted microbicidal activity. Surprisingly, interleukin-12 (IL-12) restored NKp30 expression and fungal killing. Thus, the NKp30 receptor plays a critical role in NK cell antifungal cytotoxicity, and diminished expression of NKp30 is responsible for defective antifungal activity of NK cells from HIV-infected patients, which can be corrected with IL-12.
authors.affiliation: Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB T2N 4N1, Canada; The Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Shu Shun
authors.initials: SS
authors.lastname: Li
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Kyei
authors.forename: Martina
authors.initials: M
authors.lastname: Timm-McCann
authors.forename: Henry
authors.initials: H
authors.lastname: Ogbomo
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Jones
authors.forename: Meiqing
authors.initials: M
authors.lastname: Shi
authors.forename: Richard F
authors.initials: RF
authors.lastname: Xiang
authors.forename: Paul
authors.initials: P
authors.lastname: Oykhman
authors.forename: Shaunna M
authors.initials: SM
authors.lastname: Huston
authors.forename: Anowara
authors.initials: A
authors.lastname: Islam
authors.forename: M John
authors.initials: MJ
authors.lastname: Gill
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Robbins
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Mody
mesh_terms: D002175:Candida / Q000276:immunology*; D002478:Cells, Cultured; D003454:Cryptococcus / Q000276:immunology*; D015536:Down-Regulation; D005658:Fungi; D015658:HIV Infections / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology*; D050296:Microbial Viability / Q000187:drug effects; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000096:biosynthesis*; D054353:Perforin / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D054353:Perforin; D058539:Phosphatidylinositol 3-Kinase