Clostridium perfringens ?-Toxin Impairs Innate Immunity via Inhibition of Neutrophil Differentiation.

ABSTRACT: Although granulopoiesis is accelerated to suppress bacteria during infection, some bacteria can still cause life-threatening infections, but the mechanism behind this remains unclear. In this study, we found that mature neutrophils in bone marrow cells (BMCs) were decreased in C. perfringens-infected mice and also after injection of virulence factor ?-toxin. C. perfringens infection interfered with the replenishment of mature neutrophils in the peripheral circulation and the accumulation of neutrophils at C. perfringens-infected sites in an ?-toxin-dependent manner. Measurements of bacterial colony-forming units in C. perfringens-infected muscle revealed that ?-toxin inhibited a reduction in the load of C. perfringens. In vitro treatment of isolated BMCs with ?-toxin (phospholipase C) revealed that ?-toxin directly decreased mature neutrophils. ?-Toxin did not influence the viability of isolated mature neutrophils, while simultaneous treatment of BMCs with granulocyte colony-stimulating factor attenuated the reduction of mature neutrophils by ?-toxin. Together, our results illustrate that impairment of the innate immune system by the inhibition of neutrophil differentiation is crucial for the pathogenesis of C. perfringens to promote disease to a life-threatening infection, which provides new insight to understand how pathogenic bacteria evade the host immune system.

SUBMITTER: Takehara M 

PROVIDER: S-EPMC4910053 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature