Probing the function of Bordetella bronchiseptica adenylate cyclase toxin by manipulating host immunity
Probing the function of Bordetella bronchiseptica adenylate cyclase toxin by manipulating host immunity
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DOI：
10.1128/iai.67.3.1493-1500.1999
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发表时间：
1999-03-01
影响因子：
3.1
通讯作者：
Miller, JF
中科院分区：
文献类型：
--
作者：
Harvill, ET;Cotter, PA;Miller, JF
我们已经研究了腺苷酸环化酶溶血素（CyaA）的作用，通过构建一个框内缺失的支气管败血波氏杆菌cyaA结构基因，并比较野生型和cyaA缺失菌株在自然宿主感染模型。野生型菌株RB 50及其腺苷酸环化酶毒素缺失（Delta cyaA）衍生物在低剂量接种后有效地在兔、大鼠和小鼠中建立持续感染。相比之下，接种协议，种子下呼吸道发现显着差异的细菌数量和多形核白细胞的招聘在肺部从接种后5至12天。接下来，我们探索了解除免疫系统的特定方面对野生型和Delta cyaA细菌的相对表型的影响。SCID、SCID-beige或RAG-1（-/-）小鼠在高剂量或低剂量鼻内接种野生型菌株而非Delta cyaA突变体后死于致死性全身感染。通过环磷酰胺治疗或通过粒细胞集落刺激因子基因座敲除突变使小鼠出现血小板减少症，对野生型或Delta cyaA菌株的致死性感染高度敏感。这些结果揭示了中性粒细胞在B早期所起的重要作用。支气管败血症感染和获得性免疫在以后的时间点，并表明吞噬细胞是一个主要的体内目标的博德特氏菌腺苷酸环化酶毒素。
We have examined the role of adenylate cyclase-hemolysin (CyaA) by constructing an in-frame deletion in the Bordetella bronchiseptica cyaA structural gene and comparing wild-type and cyaA deletion strains in natural host infection models. Both the wild-type strain RB50 and its adenylate cyclase toxin deletion (Delta cyaA) derivative efficiently establish persistent infections in rabbits, rats, and mice following low-dose Inoculation. In contrast, an inoculation protocol that seeds the lower respiratory tract revealed significant differences in bacterial numbers and in polymorphonuclear neutrophil recruitment in the lungs from days 5 to 12 postinoculation. We next explored the effects of disarming specific aspects of the immune system on the relative phenotypes of wild-type and Delta cyaA bacteria. SCID, SCID-beige, or RAG-1(-/-) mice succumbed to lethal systemic infection following high- or low-dose intranasal inoculation with the wild-type strain but not the Delta cyaA mutant. Mice rendered neutropenic by treatment with cyclophosphamide or by knockout mutation in the granulocyte colony-stimulating factor locus were highly susceptible to lethal infection by either wild-type or Delta cyaA strains. These results reveal the significant role played by neutrophils early in B. bronchiseptica infection and by acquired immunity at later time points and suggest that phagocytic cells are a primary in vivo target of the Bordetella adenylate cyclase toxin.