IL-12 Restores Defective NK Cell Anticryptococcal Activity in HIV-Infected Patients
Date
2015-04-30
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Cryptococcus neoformans is a pathogenic yeast that causes life-threatening pneumonia and meningitis in AIDS patients. Natural killer (NK) cells are important effector cells that directly recognize and kill C. neoformans via perforin-dependent cytotoxicity. Although it had previously been demonstrated that, NK cells from HIV-infected patients have defective anticryptococcal activity, and IL-12 restored the activity, almost nothing was known of the mechanisms causing this defect or how IL-12 restored the defect. By examining the sequential steps in NK cell killing of Cryptococcus, I determined that NK cells from HIV-infected patients had lower intracellular perforin expression, defective perforin release and defective ability to polarize perforin to the fungal synapse. Importantly, treatment of NK cells from HIV-infected patients with IL-12 reversed these defects and restored the defective anticryptococcal activity. Thus, there are multiple defects in the cytolytic machinery of NK cells from HIV-infected patients, which result in the defective anticryptococcal activity, and these defects can be reversed with IL-12.
Description
Keywords
Immunology
Citation
Kyei, S. K. (2015). IL-12 Restores Defective NK Cell Anticryptococcal Activity in HIV-Infected Patients (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26443