Final Report Summary - BACNK (Recognition of bacteria by NK cells)
We know very little about the interactions between NK cells and bacteria and fungi and the most fundamental questions in this field remain largely unknown. We do not know how many intracellular and extracellular bacteria are recognized by NK cells, whether NK cells recognize gram positive or gram negative bacteria, whether anaerobic, or aerobic bacteria are recognized, how bacteria are recognized and what are the functional consequences of such recognition. Similarly, questions exist regarding fungi. In short we do not understand the rules governing the interaction between specific NK cell receptors bacteria and fungi.
Using a systematic screen of bacteria that interact with NK cells and mutagenesis approach, we found that Uropathogenic Escherichia coli (UPEC) adheres to NK cells primarily via its type I fimbriae and employs its hemolysinA toxin to kill NK cells.
We also showed that Fusobacterium nucleatum inhibits the activity of immune cells by binding to human, but not by mouse TIGIT, an inhibitory receptor present on all human NK cells and on various T cells. In additon we discovered that Candida Glabrata is directly recognized and killed by NK cells via the interaction of NKp46 (Ncr1) in mice with the Candida Glabrata EPA proteins.