| First Author | Takehara M | Year | 2019 |
| Journal | Commun Biol | Volume | 2 |
| Pages | 45 | PubMed ID | 30729183 |
| Mgi Jnum | J:278521 | Mgi Id | MGI:6356285 |
| Doi | 10.1038/s42003-019-0280-2 | Citation | Takehara M, et al. (2019) Clostridium perfringens alpha-toxin impairs granulocyte colony-stimulating factor receptor-mediated granulocyte production while triggering septic shock. Commun Biol 2:45 |
| abstractText | During bacterial infection, granulocyte colony-stimulating factor (G-CSF) is produced and accelerates neutrophil production from their progenitors. This process, termed granulopoiesis, strengthens host defense, but Clostridium perfringens alpha-toxin impairs granulopoiesis via an unknown mechanism. Here, we tested whether G-CSF accounts for the alpha-toxin-mediated impairment of granulopoiesis. We find that alpha-toxin dramatically accelerates G-CSF production from endothelial cells in response to Toll-like receptor 2 (TLR2) agonists through activation of the c-Jun N-terminal kinase (JNK) signaling pathway. Meanwhile, alpha-toxin inhibits G-CSF-mediated cell proliferation of Ly-6G(+) neutrophils by inducing degradation of G-CSF receptor (G-CSFR). During sepsis, administration of alpha-toxin promotes lethality and tissue injury accompanied by accelerated production of inflammatory cytokines in a TLR4-dependent manner. Together, our results illustrate that alpha-toxin disturbs G-CSF-mediated granulopoiesis by reducing the expression of G-CSFR on neutrophils while augmenting septic shock due to excess inflammatory cytokine release, which provides a new mechanism to explain how pathogenic bacteria modulate the host immune system. |
