Arginine metabolism and T cell function in severe infection

I wish to understand why different patients with the same initial insult can have wildly different outcomes in Intensive Care.

Poorer outcomes are associated with higher rates of hospital-acquired infection from ‘opportunistic’ organisms that cause disease in patients with defective immune systems.

One example is the detection of herpesviruses in critically ill adults on ICU, viruses that don’t usually trouble patients with intact immune systems.

Their presence strongly suggests a problem with T-cell immunity, immune cells that are critical for controlling herpesvirus infections.

Defective T-cells are detected in sepsis (life-threatening infection), but also in other causes of critical illness including major trauma.

I will investigate the mechanisms underlying impaired T-cell function in order to identify future drug targets to liberate this suppressed arm of the immune system.

I will study the metabolism of the amino acid arginine because 1) this amino acid vital for normal T-cell function and 2) preliminary data suggests that sepsis is associated with increased arginine breakdown.

I will use a combination of approaches to interrogate the hypothesis that increased breakdown of arginine by the enzyme arginase drives suppression of T-cell function in severe infection.