FoxO3a Signaling Promotes the Inflammatory Response During Salmonella Typhimurium Infection

Abstract

FoxO3a is a transcription factor that regulates various cellular functions such as cell cycle or cell death. However, its role in the innate immune response is not clear. I investigated the impact of FoxO3a signaling on the immune response during infection with Salmonella Typhimurium (ST). My results revealed that FoxO3a regulated the homeostasis of myeloid cells in the spleen and blood of mice during steady-state. Following infection of macrophages with ST, FoxO3a signaling promoted the expression of pro-inflammatory cytokines such as IL12 and TNFα, but inhibited the expression of the anti-inflammatory cytokine IL10. Phenotypic analysis revealed that FoxO3a signaling had no effect on classical macrophage polarization into M1 vs M2 phenotypes, although it appeared to regulate mitochondrial function during infection with ST. Inflammatory responses are critical during infection with virulent intracellular pathogens, and these results provide new insights into the role of FoxO3a signaling in inflammatory responses.