UNdersTanding how viRAl Infections shape NK cElls Diversity – Untrained

Natural killer (NK) cells are implicated in the control of tumors and viral infections, including HIV-1 infection. NK cell activity is tightly controlled through the balance of a large repertoire of inhibitory and activating
receptors. In the last years, the new-generation technologies allowed to uncover that the spectrum of human NK cell diversity is even much broader than originally appreciated. The recent discoveries of the capacity for NK cells to adapt and also to differentiate into long-lived memory cells has added further complexity to this
field. Memory-like NK cells can be generated by stimulation with IL-12/15/18. Altogether, this raises the possibility that there are unexpected functional specialization and distinct adaptive capabilities among NK cell subpopulations in response to viral infections and immunizations, a mechanism which could be exploited to promote anti-viral immunity. Most studies have focused on blood. As for T cells, the importance for a better understanding of the tissue-specific functions of NK cells have though increasingly being appreciated.
Here, we propose to better understand how NK cells acquire the capacity to eliminate infected cells by using
the nonhuman primate models. Our specific goals are: 1) to identify the anatomical site of generation of adaptive NK cells during viral infection; 2) to determine the phenotypical and molecular NK cell determinants in early infection in tissues
to better understand why in some cases tissue NK cells do not develop the capacity to control viral infection in tissues ; 3) to determine the differences in tissue microenvironments viral infections by focusing on molecules that might have an impact on NK cell profiles and activity.
Through the comprehensive analyses of tissue NK cells in these models, we aim to better understand
biological processes promoting or blocking the generation of efficient NK cells against viral infected cells.