Bacterial Toxins and Therapeutics Section, Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Host Microbe. 2010 Nov 18;8(5):455-62. doi: 10.1016/j.chom.2010.10.004.
Bacillus anthracis kills through a combination of bacterial infection and toxemia. Anthrax toxin working via the CMG2 receptor mediates lethality late in infection, but its roles early in infection remain unclear. We generated myeloid-lineage specific CMG2-deficient mice to examine the roles of macrophages, neutrophils, and other myeloid cells in anthrax pathogenesis. Macrophages and neutrophils isolated from these mice were resistant to anthrax toxin. However, the myeloid-specific CMG2-deficient mice remained fully sensitive to both anthrax lethal and edema toxins, demonstrating that targeting of myeloid cells is not responsible for anthrax toxin-induced lethality. Surprisingly, the myeloid-specific CMG2-deficient mice were completely resistant to B. anthracis infection. Neutrophil depletion experiments suggest that B. anthracis relies on anthrax toxin secretion to evade the scavenging functions of neutrophils to successfully establish infection. This work demonstrates that anthrax toxin uptake through CMG2 and the resulting impairment of myeloid cells are essential to anthrax infection.
炭疽杆菌通过细菌感染和毒血症的结合来致死。炭疽毒素通过 CMG2 受体发挥作用，在感染后期介导致死性，但在感染早期的作用仍不清楚。我们生成了骨髓谱系特异性 CMG2 缺陷小鼠，以研究巨噬细胞、中性粒细胞和其他髓样细胞在炭疽病发病机制中的作用。从这些小鼠中分离出的巨噬细胞和中性粒细胞对炭疽毒素具有抗性。然而，骨髓特异性 CMG2 缺陷小鼠对炭疽致死毒素和水肿毒素仍然完全敏感，表明针对髓样细胞并不是炭疽毒素诱导致死的原因。令人惊讶的是，骨髓特异性 CMG2 缺陷小鼠对炭疽杆菌感染完全具有抗性。中性粒细胞耗竭实验表明，炭疽杆菌依赖炭疽毒素的分泌来逃避中性粒细胞的清除功能，从而成功建立感染。这项工作表明，炭疽毒素通过 CMG2 的摄取以及由此对髓样细胞的损害，是炭疽感染所必需的。
