Exercise-mediated changes in plasmacytoid dendritic cell production of IFNα and the effects of moderate intensity exercise on immune response to influenza infection and influenza vaccine

Epidemiological studies suggest that moderate exercise is associated with improved resistance to infection; it has also been shown that acute exhaustive exercise is associated with increased susceptibility to infection, particularly upper respiratory tract infections. Seasonal influenza virus is a contagious upper respiratory tract infection that can lead to widespread morbidity and mortality each year, despite the availability of a vaccine for influenza. Type I interferons (IFNs) are one of the body\u27s first lines of defense against viral infection. Influenza vaccines containing interferon-alpha (IFNa) have been shown to increase antigen-specific antibody titer. The purpose of the experiments carried out in this dissertation were to first determine a possible mechanism for the increase in infection resistance seen after moderate exercise as well as the decline in resistance to infection post exhaustive exercise, and second to determine the role exercise might play in the response to influenza vaccination. The first group of experiments tested the effect of different durations of exercise on the production of IFNa by influenza-stimulated plasmacytoid dendritic cells. Levels of IFNa were shown to be significantly increased after 90min of exercise but significantly decreased after 180min of exercise. The temporary exercise-induced increase in antiviral function by pDCs may contribute to the reduction of infection observed in regular exercisers. There was also a greater increase in IFNa production in cells stimulated with norepinephrine or epinephrine compared to control. The second set of experiments tested the effects of exercise immediately following influenza vaccination on the immune system. Subjects exercising for 90min immediately following influenza vaccination showed a significantly greater antigen specific antibody response at 2 and 4 weeks post vaccination. Subjects that reported the greatest levels of stress also had the smallest increases in antibody. In the third set of experiments, the duration of exercise post vaccination as well as specific mechanisms of action were tested. Mice who exercised for 90min post vaccination showed significantly greater antibody responses to vaccination than 0, 45 or 180min of exercise at 4 weeks post vaccination. Exercise mice also showed significantly greater levels of antigen- experienced CD4 and CD8 T cells compared to the no exercise group. The findings from these three separate experiments show that moderate intensity exercise induced increases in IFNa; and that moderate intensity exercise for 90min might be used as a vaccine adjuvant if performed immediately post vaccination