Clostridium perfringens α-Toxin Impairs Innate Immunity via Inhibition of Neutrophil Differentiation.
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.
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Masaya
M
Takehara
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Teruhisa
T
Takagishi
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Soshi
S
Seike
Department of Bacteriology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa 920-8640, Japan.|Miyarisan Pharmaceutical Co., LTD, 1-10-3, Kaminakazato, Kita-ku, Tokyo 114-0016, Japan.
Kaori
K
Ohtani
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Keiko
K
Kobayashi
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Kazuaki
K
Miyamoto
Department of Bacteriology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa 920-8640, Japan.
Tohru
T
Shimizu
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
Masahiro
M
Nagahama
D000818:Animals; D001412:Bacillus subtilis / Q000235:genetics / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000235:genetics / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003015:Clostridium Infections / Q000473:pathology; D003016:Clostridium perfringens / Q000235:genetics / Q000472:pathogenicity*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology; D009504:Neutrophils / Q000276:immunology*; D010738:Type C Phospholipases / Q000235:genetics / Q000633:toxicity*; D037521:Virulence Factors / Q000235:genetics / Q000633:toxicity*
D001427:Bacterial Toxins; D002135:Calcium-Binding Proteins; D037521:Virulence Factors; D016179:Granulocyte Colony-Stimulating Factor; D010738:Type C Phospholipases; C040649:alpha toxin, Clostridium perfringens