Enhanced Neutrophil Longevity and Recruitment Contribute to the Severity of Oviduct Pathology during Chlamydia muridarum Infection
Enhanced Neutrophil Longevity and Recruitment Contribute to the Severity of Oviduct Pathology during Chlamydia muridarum Infection
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DOI：
10.1128/iai.05535-11
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发表时间：
2011-10-01
影响因子：
3.1
通讯作者：
Darville, Toni
中科院分区：
文献类型：
--
作者：
Frazer, Lauren C.;O'Connell, Catherine M.;Darville, Toni
我们之前的研究表明，小鼠阴道内感染鼠衣原体质粒缺陷菌株 CM3.1 不会诱发输卵管病变。在这项研究中，我们确定 CM3.1 感染会导致急性感染期间输卵管中中性粒细胞的频率和绝对数量显着降低。中性粒细胞的减少与输卵管中中性粒细胞趋化因子水平的显着降低以及体外感染CM3.1的输卵管上皮细胞产生的中性粒细胞趋化因子的减少相关。 CM3.1 感染还导致输卵管中晚期凋亡/死亡中性粒细胞的频率增加。沙眼衣原体体外预防中性粒细胞凋亡能力的检测表明，与质粒缺陷型 CTD153 相比，沙眼衣原体菌株 D/UW-3/Cx 表现出增强的预防中性粒细胞凋亡的能力，并且这种作用依赖于 CD14(高) 单核细胞的存在。相对于 CTD153 的结果，单核细胞的存在还导致中性粒细胞细胞因子的产生增强，并且响应 D/UW-3/Cx 的组织损伤分子的产生增加。尝试使用抗体介导的耗竭来辨别中性粒细胞在体内感染控制和病理学中的具体作用表明，尽管通过这种治疗从血液和输卵管中消除了Ly6G（高）中性粒细胞，但在上生殖道中仍然可以检测到未成熟的中性粒细胞和高水平的组织损伤分子。这些数据支持中性粒细胞在衣原体诱导的病理学中的作用，并揭示在体内具体确定其作用之前必须开发新的消耗方法。
Our previous studies revealed that intravaginal infection of mice with a plasmid-deficient strain of Chlamydia muridarum, CM3.1, does not induce the development of oviduct pathology. In this study, we determined that infection with CM3.1 resulted in a significantly reduced frequency and absolute number of neutrophils in the oviducts during acute infection. This reduction in neutrophils was associated with significantly lower levels of neutrophil chemokines in the oviducts and decreased production of neutrophil chemokines by oviduct epithelial cells infected with CM3.1 in vitro. Infection with CM3.1 also resulted in an increased frequency of late apoptotic/dead neutrophils in the oviduct. Examination of the ability of Chlamydia trachomatis to prevent neutrophil apoptosis in vitro revealed that C. trachomatis strain D/UW-3/Cx exhibited an enhanced ability to prevent neutrophil apoptosis compared to plasmid-deficient CTD153, and this effect was dependent on the presence of CD14(high) monocytes. The presence of monocytes also resulted in enhanced neutrophil cytokine production and increased production of tissue-damaging molecules in response to D/UW-3/Cx relative to results with CTD153. Attempts to use antibody-mediated depletion to discern the specific role of neutrophils in infection control and pathology in vivo revealed that although Ly6G(high) neutrophils were eliminated from the blood and oviducts with this treatment, immature neutrophils and high levels of tissue-damaging molecules were still detectable in the upper genital tract. These data support the role of neutrophils in chlamydia-induced pathology and reveal that novel methods of depletion must be developed before their role can be specifically determined in vivo.