The project used mouse models of inflammation and bacterial infection to track what NK cells do from the first hours of illness to later stages. It found that NK cells respond in two waves. The first wave begins quickly (3-6 hours after the challenge), when NK cells release inflammatory molecules, such as interferon-γ and granzyme B, to fight infection. The second wave happens later (1-2 days after the challenge) and supports the growth and full activation of these cells, including production of cytotoxic molecule perforin.
A key discovery is that NK cells rely heavily on taking up certain amino acids from the bloodstream to function properly. One transporter, called Slc7a5, turned out to be essential. When NK cells lacked this transporter, they could no longer produce key factors, such as interferon-γ and granzyme B, or support inflammation. This transporter can also be targeted therapeutically using specific inhibitor to reach the similar effect. In contrast, genetic inactivation of Slc1a5 transporter did not substantially affect NK-cell response. However, therapeutic blocking of this transporter resulted in reduced production of granzyme B and perforin by NK cells.
The project also measured amino acids in the blood during inflammation and found that methionine, an amino acid needed for both energy and cell regulation, drops sharply early in sepsis. Experiments showed that lowering methionine levels weakens NK-cell activity, while adding extra methionine boosts some of their protective functions. Overall, the findings show that NK cells adjust their behaviour based on the nutrients available in the body during infection.
