Journal
SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep28192
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Grants-in-Aid for Scientific Research [15K19099, 15K08460] Funding Source: KAKEN
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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 alpha-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 alpha-toxin-dependent manner. Measurements of bacterial colony-forming units in C. perfringens-infected muscle revealed that alpha-toxin inhibited a reduction in the load of C. perfringens. In vitro treatment of isolated BMCs with alpha-toxin (phospholipase C) revealed that alpha-toxin directly decreased mature neutrophils. alpha-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 alpha-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.
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