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NK cells use perforin rather than granulysin for anticryptococcal activity.
Ling Ling Ma1, Christopher L C Wang, Graham G Neely
1Department of Medical Sciences, University of Calgary, Alberta, Canada.
Journal of Immunology (Baltimore, Md. : 1950)
|August 24, 2004
Summary
Natural killer (NK) cells possess inherent antifungal activity against Cryptococcus neoformans, primarily utilizing perforin, not granulysin, for microbial killing. This contrasts with CD8 T cells, which require activation and rely on granulysin.
Area of Science:
- Immunology
- Microbiology
- Cellular Biology
Background:
- Cytotoxic lymphocytes kill microbes, but mechanisms are unclear.
- CD8 T cells use granulysin, not perforin, for antifungal killing of Cryptococcus neoformans.
- NK cell antimicrobial mechanisms, including granulysin and perforin roles, are unknown.
Purpose of the Study:
- Investigate the mechanisms of NK cell-mediated antifungal activity.
- Determine the roles of granulysin and perforin in NK cell killing of Cryptococcus neoformans.
- Compare NK cell and CD8 T cell antifungal mechanisms.
Main Methods:
- Primary human NK cells and YT cell line were used.
- Granulysin and perforin were blocked using small interfering RNA and concanamycin A.
- Antifungal activity against Cryptococcus neoformans was measured.
Main Results:
- NK cells constitutively express granulysin and perforin, exhibiting antifungal activity without stimulation.
- Perforin, not granulysin, is essential for NK cell antifungal activity.
- NK cell antifungal activity relies on perforin, unlike CD8 T cells which depend on granulysin.
Conclusions:
- NK cells possess constitutive antifungal activity against Cryptococcus neoformans.
- Perforin is the key mediator of NK cell antifungal activity, while granulysin is dispensable.
- Distinct mechanisms govern NK cell and CD8 T cell-mediated antifungal responses.