Anthrax toxin targeting of myeloid cells through the CMG2 receptor is essential for establishment of Bacillus anthracis infections in mice.
Anthrax toxin targeting of myeloid cells through the CMG2 receptor is essential for establishment of Bacillus anthracis infections in mice.
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DOI：
10.1016/j.chom.2010.10.004
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发表时间：
2010-11-18
影响因子：
30.3
通讯作者：
Leppla SH
中科院分区：
文献类型：
--
作者：
Liu S;Miller-Randolph S;Crown D;Moayeri M;Sastalla I;Okugawa S;Leppla SH
炭疽杆菌通过细菌感染和毒血症的结合来杀死人。炭疽毒素通过CMG2受体介导感染后期的致死性，但其在感染早期的作用仍不清楚。我们产生了骨髓谱系特异性CMG2缺陷小鼠，以研究巨噬细胞，中性粒细胞和其他骨髓细胞在炭疽发病机制中的作用。从这些小鼠中分离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缺陷小鼠仍然对炭疽致死毒素和水肿毒素完全敏感，表明靶向骨髓细胞不负责炭疽毒素诱导的致死性。令人惊讶的是，骨髓特异性CMG 2缺陷小鼠对B完全耐药。炭疽感染。中性粒细胞耗竭实验表明，B.炭疽病依靠炭疽毒素分泌来逃避嗜中性粒细胞的清除功能，以成功地建立感染。这项工作表明，炭疽毒素通过CMG 2的摄取和由此产生的骨髓细胞，特别是中性粒细胞的损害，是必要的炭疽感染。
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 specifically neutrophils, is essential to anthrax infection.
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尖端：对NALP1B/NLRP1B的致命毒素敏感等位基因介导的对炭疽芽孢杆菌感染的抗性。
DOI：
10.4049/jimmunol.0903114
发表时间：
2010-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Terra JK;Cote CK;France B;Jenkins AL;Bozue JA;Welkos SL;LeVine SM;Bradley KA
通讯作者：
Bradley KA
DOI：
10.1073/pnas.0431098100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Scobie, HM;Rainey, GJA;Young, JAT
通讯作者：
Young, JAT
影响因子：
3.4
作者：
Hu, Haijing;Sa, Qila;Zhou, Daoguo
通讯作者：
Zhou, Daoguo
影响因子：
3.1
作者：
FRIEDLANDER, AM;BHATNAGAR, R;SINGH, Y
通讯作者：
SINGH, Y
DOI：
10.1073/pnas.79.10.3162
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LEPPLA, SH
通讯作者：
LEPPLA, SH