Differential roles of regulatory T cells in acute respiratory infections

Acute respiratory infections trigger an inflammatory immune response with the goal of pathogen clearance; however, overexuberant inflammation causes tissue damage and impairs pulmonary function. CD4(+)FOXP3(+) regulatory T cells (Tregs) interact with cells of both the innate and the adaptive immune system to limit acute pulmonary inflammation and promote its resolution. Tregs also provide tissue protection and coordinate lung tissue repair, facilitating a return to homeostatic pulmonary function. Here, we review Treg-mediated modulation of the host response to respiratory pathogens, focusing on mechanisms underlying how Tregs promote resolution of inflammation and repair of acute lung injury. We also discuss potential strategies to harness and optimize Tregs as a cellular therapy for patients with severe acute respiratory infection and discuss open questions in the field.