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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 α-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 α-toxin-dependent manner. Measurements of bacterial colony-forming units in  C. perfringens -infected muscle revealed that α-toxin inhibited a reduction in the load of  C. perfringens .  In vitro  treatment of isolated BMCs with α-toxin (phospholipase C) revealed that α-toxin directly decreased mature neutrophils. α-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 α-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.

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