Effects of Viable and Heat-Killed Salmonella enterica Administration on the Reduction of Exercise Performance in Mice

Abstract

Salmonella enterica, a gram negative bacteria, uses specific virulence mechanisms that cause enteritis, systemic infection, and fever. It is known that macrophages respond better to nonmotile, killed bacteria than to living or motile bacteria. TNF-α production and signal transduction also varies dependent on whether live vs. heat-killed Salmonella is administered. Although LPS of Salmonella is recognized by toll-like receptor (TLR) 4 on the outer membrane of immune cells, it is not clear whether a reduction in physical activity seen after infection occurs via TLR4 recognition. PURPOSE: The purpose of this study was to determine whether living or heat-killed Salmonella administration regulates the reduction of voluntary physical activity in mice. Our hypothesis was that a reduction in physical activity would not be induced by live Salmonella infection. METHODS: In this study, we used C3H/HeN mice. Salmonella enterica serovar Dublin was grown for 48 h at 35°C in a brain heart agar medium and administered as live bacteria (2×104CFU/mouse i.p.) or as heat-killed Salmonella (same dose treated at 62°C for 2 hrs). Survival rate was monitored for 10 days and the level of infection in the kidney was assessed in infected animals at days 2 and 10 in infected mice. Voluntary physical activity in both groups of mice was examined by observing their running performance in a cage-adjacent wheel for 2 days after i.p. injection. In vitro peritoneal macrophage production of TNF-α was measured by ELISA assay under both living and heat-killed Salmonella conditions. RESULTS: Live Salmonella injection reduced survival of mice, but heat-killed Salmonella did not (p<0.01). Paradoxically, voluntary physical activity in heat-killed Salmonella injected mice was significantly lower than that in live Salmonella injected mice (p<0.05). Furthermore, TNF-α production from isolated peritoneal macrophages in mice was shown to be different between living and heat-killed Salmonella conditions. CONCLUSION: Our findings suggest that heat-killed Salmonella induces the reduction of voluntary physical activity in mice, but living Salmonella does not. Accordingly, physical activity in the early phase after infection might be regulated by immuno response depend on bacteria fragments.