Coxiella burnetii Acid Phosphatase Inhibits the Release of Reactive Oxygen Intermediates in Polymorphonuclear Leukocytes
Coxiella burnetii Acid Phosphatase Inhibits the Release of Reactive Oxygen Intermediates in Polymorphonuclear Leukocytes
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DOI：
10.1128/iai.01011-10
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发表时间：
2011-01-01
影响因子：
3.1
通讯作者：
Samuel, J. E.
中科院分区：
文献类型：
--
作者：
Hill, J.;Samuel, J. E.
Q热的病原体贝氏柯克斯体是一种小型革兰氏阴性专性胞内细菌。C.通过使用p47 phox（-/-）和iNOS（-/-）小鼠在体内降低氧化应激和通过体外药理学抑制剂，已经显示感染期间的贝氏体的感染增加。在此模型的基础上，我们研究了多形核白细胞（PMN）在控制感染中的作用，因为NADPH氧化酶介导的活性氧中间体（ROI）的释放是这些细胞的主要杀菌机制，对早期先天性清除至关重要。早期的研究表明C. Burnetii通过表达一种未鉴定的酸性磷酸酶（ACP）来抑制PMN释放ROI。最近的基因组注释鉴定了一个开放阅读框（CBU 0335），其可能编码Sec-和II型依赖性分泌型ACP。为了验证该模型，可行的C。在组织培养宿主细胞或无菌培养基中繁殖的贝氏隐翅虫C.将贝氏提取物或纯化的重组ACP（rACP）与用4-佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的人PMN组合。用C. burnetii，C.贝氏提取物或rACP，但当PMN用电子束灭活的C.伯内特氏菌C. burnetii提取物和rACP也能够抑制PMA诱导的PMN膜上NADPH氧化酶复合物的形成，表明这种抑制的分子机制。这些数据支持一个模型，其中C。贝氏体通过分泌至少一种酸性磷酸酶来逃避活化PMN的主要ROI杀伤机制。
Coxiella burnetii, the etiological agent of Q fever, is a small, Gram-negative, obligate intracellular bacterium. Replication of C. burnetii during infection has been shown to be increased by decreasing oxidative stress using p47phox(-/-) and iNOS(-/-) mice in vivo and by pharmacologic inhibitors in vitro. Building upon this model, we investigated the role polymorphonuclear leukocytes (PMN) play in the control of infection, since NADPH oxidase-mediated release of reactive oxygen intermediates (ROI) is a primary bactericidal mechanism for these cells that is critical for early innate clearance. Earlier studies suggested that C. burnetii actively inhibited release of ROI from PMN through expression of an unidentified acid phosphatase (ACP). Recent genomic annotations identified one open reading frame (CBU0335) which may encode a Sec-and type II-dependent secreted ACP. To test this model, viable C. burnetii propagated in tissue culture host cells or axenic media, C. burnetii extracts, or purified recombinant ACP (rACP) was combined with human PMN induced with 4-phorbol 12-myristate 13-acetate (PMA). The release of ROI was inhibited when PMN were challenged with viable C. burnetii, C. burnetii extracts, or rACP but not when PMN were challenged with electron beam-inactivated C. burnetii. C. burnetii extracts and rACP were also able to inhibit PMA-induced formation of NADPH oxidase complex on PMN membranes, suggesting a molecular mechanism responsible for this inhibition. These data support a model in which C. burnetii eludes the primary ROI killing mechanism of activated PMN by secreting at least one acid phosphatase.