The Journal of biological chemistry, 25 March 2016, Vol.291(13), pp.6912-22
The activity of Rac in leukocytes is essential for immunity. However, its role in NK cell-mediated anti-microbial signaling remains unclear. In this study, we investigated the role of Rac in NK cell mediated anti-cryptococcal killing. We found thatCryptococcus neoformansindependently activates both Rac and SFK pathways in NK cells, and unlike in tumor killing,Cryptococcusinitiated a novel Rac → PI3K → Erk cytotoxicity cascade. Remarkably, Rac was not required for conjugate formation, despite its essential role in NK cytotoxicity againstC. neoformans Taken together, our data show that, unlike observations with tumor cells, NK cells use a novel Rac cytotoxicity pathway in conjunction with SFK, to killC. neoformans.
Cellular Signaling ; Cryptococcus ; Rac (Rac Gtpase) ; Src ; Adhesion ; Fungi ; Natural Killer Cells (Nk Cells) ; Phosphatidylinositide 3-Kinase (PI 3-Kinase) ; Cytotoxicity, Immunologic ; Class Ia Phosphatidylinositol 3-Kinase -- Immunology ; Cryptococcus Neoformans -- Physiology ; Killer Cells, Natural -- Immunology ; Rac Gtp-Binding Proteins -- Immunology ; Rac1 Gtp-Binding Protein -- Immunology ; Src-Family Kinases -- Immunology
View this record in MEDLINE/PubMed