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Neutrophil extracellular traps prevent HIV infection in the female genital tract.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2018-09-01 , DOI: 10.1038/s41385-018-0045-0
Fiona D Barr 1 , Christina Ochsenbauer 2 , Charles R Wira 1 , Marta Rodriguez-Garcia 1
Affiliation  

Women acquire human immunodeficiency virus (HIV) mainly through sexual intercourse. However, low transmission rates per sexual act indicate that local immune mechanisms contribute to HIV prevention. Neutrophils represent 10-20% of the genital immune cells in healthy women. Neutrophils mediate mucosal protection against bacterial and fungal pathogens through different mechanisms, including the release of neutrophil extracellular traps (NETs). NETs are DNA fragments associated with antimicrobial granular proteins. Despite neutrophil abundance and central contributions to innate immunity in the genital tract, their role in protection against HIV acquisition is unknown. We found that stimulation of human genital neutrophils with HIV viral-like particles (HIV-VLPs) induced NET release within minutes of viral exposure, through reactive oxygen species-independent mechanisms that resulted in immediate entrapment of HIV-VLPs. Incubation of infectious HIV with pre-formed genital NETs prevented infection of susceptible cells through irreversible viral inactivation. HIV inactivation by NETs from genital neutrophils could represent a previously unrecognized form of mucosal protection against HIV acquisition.

中文翻译:

中性粒细胞胞外陷阱可防止女性生殖道中的 HIV 感染。

女性主要通过性交感染人类免疫缺陷病毒(HIV)。然而,每次性行为的低传播率表明局部免疫机制有助于预防艾滋病毒。中性粒细胞占健康女性生殖器免疫细胞的 10-20%。中性粒细胞通过不同的机制介导粘膜对细菌和真菌病原体的保护,包括释放中性粒细胞胞外陷阱 (NETs)。NET 是与抗菌颗粒蛋白相关的 DNA 片段。尽管嗜中性粒细胞丰富且对生殖道先天免疫有重要贡献,但它们在预防 HIV 感染中的作用尚不清楚。我们发现,用 HIV 病毒样颗粒 (HIV-VLP) 刺激人类生殖器嗜中性粒细胞会在病毒暴露后几分钟内诱导 NET 释放,通过独立于活性氧的机制,导致 HIV-VLP 立即被捕获。用预先形成的生殖器 NET 孵育传染性 HIV,可通过不可逆的病毒灭活来预防易感细胞的感染。NETs 从生殖器嗜中性粒细胞灭活 HIV 可能代表一种以前未被识别的粘膜保护形式,可防止 HIV 感染。
更新日期:2018-06-06
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