Antibacterial activity of human natural killer cells in the absence of accessory cells against extracellular Staphylococcus aureus and hypervirulent Pseudomonas aeruginosa bacteria

Abstract

Natural killer (NK) cells play a crucial role in the innate immune response to bacterial infections, including those due to Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). In vivo, it has been shown that NK cells are activated by innate accessory cells that detect the presence of bacteria and activate NK cells via a cytokine network. In vitro, several studies have shown that NK cells can also be activated without the help of accessory cells by direct contact with some bacteria species such as extracellular P. aeruginosa. Whether this phenomenon of direct activation is restricted to certain bacterial species, or whether it can be generalized, is still debated, as for example in the case of NK cell activation by S. aureus, which seems to require the intervention of accessory immune cells. Here, we show with co-incubation experiments between NK cells and two bacterial species, that, in the absence of accessory cells, NK cells are able to impede bacterial growth. This has been demonstrated for the P. aeruginosa PA14 strain, which is hypervirulent and known for its deleterious effects on NK cells, as well as for the S. aureus Newman strain. The monitoring of CD107a by flow cytometry suggests that NK cells degranulate after contact with S. aureus bacteria. Our study contributes to the idea that NK cells can be activated in the absence of any accessory cells by various species of bacteria, even an hypervirulent one, and therefore that NKs can directly have an antibacterial effect. This important insight may pave the way for new therapeutic approaches using antibacterial NK-cell engagers.