The NK Receptor NKp30 Mediates Direct Fungal Recognition and Killing and Is Diminished in NK Cells from HIV-Infected Patients
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...
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Published in | Cell host & microbe Vol. 14; no. 4; pp. 387 - 397 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
16.10.2013
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Subjects | |
Online Access | Get full text |
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Summary: | 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.
•An unbiased approach identifies NKp30 as a NK cell fungicidal receptor•NKp30 mediates direct binding, signaling, and perforin release in response to fungi•NK cells from HIV patients had diminished NKp30 expression and blunted fungal killing•IL-12 restored NKp30 expression and fungal killing in NK cells from HIV patients |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1931-3128 1934-6069 |
DOI: | 10.1016/j.chom.2013.09.007 |