Prolonged high-intensity exercise induces fluctuating immune responses to herpes simplex virus infection via glucocorticoids.

Abstract Background Epidemiological studies have yielded conflicting results regarding the influence of a single bout of prolonged high-intensity exercise on viral infection. Objective Here, we show that prolonged high-intensity exercise induces either exacerbation or amelioration of herpes simplex virus type 2 (HSV-2) infection depending on the interval between viral exposure and exercise. Methods Mice were intravaginally infected with HSV-2 and exposed to run on the treadmill. Results Prolonged high-intensity exercise 17 h after infection impaired the clearance of HSV-2, while exercise 8 h after infection enhanced the clearance of HSV-2. These impaired or enhanced immune responses were related to a transient decrease or increase in the number of blood-circulating plasmacytoid dendritic cells (pDCs). Exercise-induced glucocorticoids transiently decreased the number of circulating pDCs by facilitating their homing to the bone marrow via the CXCL12-CXCR4 axis, which led to their subsequent increase in the blood. Conclusion Thus, a single bout of prolonged high-intensity exercise can be either deleterious or beneficial to antiviral immunity.