PMID- 27306065 OWN - NLM STAT- MEDLINE DCOM- 20180522 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Jun 16 TI - Clostridium perfringens alpha-Toxin Impairs Innate Immunity via Inhibition of Neutrophil Differentiation. PG - 28192 LID - 10.1038/srep28192 [doi] LID - 28192 AB - 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. FAU - Takehara, Masaya AU - Takehara M AD - Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan. FAU - Takagishi, Teruhisa AU - Takagishi T AD - Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan. FAU - Seike, Soshi AU - Seike S AD - Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan. FAU - Ohtani, Kaori AU - Ohtani K AD - Department of Bacteriology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa 920-8640, Japan. AD - Miyarisan Pharmaceutical Co., LTD, 1-10-3, Kaminakazato, Kita-ku, Tokyo 114-0016, Japan. FAU - Kobayashi, Keiko AU - Kobayashi K AD - Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan. FAU - Miyamoto, Kazuaki AU - Miyamoto K AD - Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan. FAU - Shimizu, Tohru AU - Shimizu T AD - Department of Bacteriology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa 920-8640, Japan. FAU - Nagahama, Masahiro AU - Nagahama M AD - Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160616 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Bacterial Toxins) RN - 0 (Calcium-Binding Proteins) RN - 0 (Virulence Factors) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - EC 3.1.4.- (Type C Phospholipases) RN - EC 3.1.4.3 (alpha toxin, Clostridium perfringens) SB - IM MH - Animals MH - Bacillus subtilis/genetics/pathogenicity MH - Bacterial Toxins/genetics/*toxicity MH - Bone Marrow Cells/*drug effects MH - Calcium-Binding Proteins/genetics/*toxicity MH - Cell Differentiation/drug effects MH - Cells, Cultured MH - Clostridium Infections/pathology MH - Clostridium perfringens/genetics/*pathogenicity MH - Granulocyte Colony-Stimulating Factor/pharmacology MH - Immunity, Innate/drug effects/*immunology MH - Leukocyte Count MH - Mice MH - Mice, Inbred C57BL MH - Muscle, Skeletal/cytology MH - Neutrophils/*immunology MH - Type C Phospholipases/genetics/*toxicity MH - Virulence Factors/genetics/*toxicity PMC - PMC4910053 EDAT- 2016/06/17 06:00 MHDA- 2018/05/23 06:00 PMCR- 2016/06/16 CRDT- 2016/06/17 06:00 PHST- 2016/03/17 00:00 [received] PHST- 2016/06/01 00:00 [accepted] PHST- 2016/06/17 06:00 [entrez] PHST- 2016/06/17 06:00 [pubmed] PHST- 2018/05/23 06:00 [medline] PHST- 2016/06/16 00:00 [pmc-release] AID - srep28192 [pii] AID - 10.1038/srep28192 [doi] PST - epublish SO - Sci Rep. 2016 Jun 16;6:28192. doi: 10.1038/srep28192.