Dai Jin, Tang Lingli, Chen Jianlin, Yu Ping, Chen Ze, Zhong Guangming
College of Life Sciences, Hunan Normal University, 36 Lushan Rd., Changsha 410081, Hunan Province, PR China; Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Second Xiangya Hospital, No. 139 Renmin Rd., Changsha 410011, Hunan Province, PR China.
Microbes Infect. 2016 Mar;18(3):190-8. doi: 10.1016/j.micinf.2015.11.003. Epub 2015 Dec 2.
The Chlamydia muridarum induction of the upper genital tract pathology in mice has been used to investigate the mechanisms of chlamydial pathogenesis. We report that the NCF1 (neutrophil cytosolic factor1)-encoded p47phox (phagocyte oxidase), an essential subunit of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, contributes significantly to C. muridarum induction of hydrosalpinx. Mice lacking p47phox (p47phox-deficient) were no longer able to develop significant hydrosalpinx following an intravaginal infection with C. muridarum. However, there was no significant difference in uterine horn dilation (as a result of the endometrial glandular duct dilation) between the p47phox-deficient and -sufficient mice. Thus, the role of NADPH oxidase in chlamydial pathogenesis is restricted to the oviduct tissue rather than the entire upper genital tract. Interestingly, both the p47phox-deficient and -sufficient mice displayed similar levels of chlamydial live organism shedding from the lower genital tract, suggesting that the NADPH oxidase is not required for the mouse control of chlamydial infection in the lower genital tract. Furthermore, the p47phox deficiency did not affect the infectious organism burden in the upper genital tract tissues, indicating that the NADPH-oxidase activity is not necessary for the mouse prevention of chlamydial ascension from the lower to upper genital tracts. However, the p47phox-defieicnt mice displayed a significantly reduced chronic inflammatory infiltration in the oviduct but not uterine tissues, supporting the finding that the NADPH oxidase activity is required for chlamydial induction of dilation in the oviduct but not the endometrial glandular duct. Thus, we have demonstrated a significant role of the host NADPH oxidase in promoting chronic inflammatory pathology in the oviduct following chlamydial infection.
鼠衣原体诱导小鼠上生殖道病变已被用于研究衣原体致病机制。我们报告称，烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶的一个必需亚基——由NCF1（中性粒细胞胞质因子1）编码的p47phox（吞噬细胞氧化酶），对鼠衣原体诱导输卵管积水有显著作用。缺乏p47phox的小鼠（p47phox缺陷型）在经阴道感染鼠衣原体后不再能够发生明显的输卵管积水。然而，p47phox缺陷型和野生型小鼠之间子宫角扩张（由于子宫内膜腺管扩张所致）并无显著差异。因此，NADPH氧化酶在衣原体致病机制中的作用仅限于输卵管组织，而非整个上生殖道。有趣的是，p47phox缺陷型和野生型小鼠从下生殖道排出的衣原体活生物体水平相似，这表明NADPH氧化酶并非小鼠控制下生殖道衣原体感染所必需。此外，p47phox缺陷并不影响上生殖道组织中的感染性生物体负荷，这表明NADPH氧化酶活性并非小鼠预防衣原体从下生殖道向上生殖道上行所必需。然而，p47phox缺陷型小鼠输卵管中的慢性炎症浸润显著减少，但子宫组织中未减少，这支持了以下发现：NADPH氧化酶活性是衣原体诱导输卵管扩张而非子宫内膜腺管扩张所必需。因此，我们证明了宿主NADPH氧化酶在衣原体感染后促进输卵管慢性炎症病理过程中发挥的重要作用。
