Schistosoma mansoni treatment reduces HIV entry into cervical CD4+ T cells and induces IFN-I pathways.
Schistosoma mansoni treatment reduces HIV entry into cervical CD4+ T cells and induces IFN-I pathways.
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曼氏血吸虫治疗可减少 HIV 进入宫颈 CD4 T 细胞并诱导 IFN-I 途径。
DOI：
10.1038/s41467-019-09900-9
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发表时间：
2019
影响因子：
16.6
通讯作者：
Kaul,Rupert
中科院分区：
文献类型：
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作者：
Yegorov,Sergey;Joag,Vineet;Galiwango,RonaldM;Good,SaraV;Mpendo,Juliet;Tannich,Egbert;Boggild,AndreaK;Kiwanuka,Noah;Bagaya,BernardS;Kaul,Rupert
曼氏血吸虫（Sm）感染与女性感染艾滋病毒的风险增加有关。因此，确定降低艾滋病毒易感性的机制可能会导致新的艾滋病毒预防策略。在这里，我们分析了标准 Sm 疗法对未感染 HIV 的 Sm+乌干达成年女性对生殖器 HIV 易感性以及粘膜和全身免疫学的影响。尽管短暂的全身和粘膜免疫激活以及生殖器 IL-1α 水平升高，但血吸虫病治疗可显着减少 HIV 进入宫颈和血液 CD4+ T 细胞的数量，这种情况可持续长达两个月。治疗后生殖器 IFN-α2a 水平也升高，并且 IFN-α2a 阻止 HIV 离体进入初级 CD4+T 细胞。 Sm治疗后血液单核细胞的转录组分析显示IFN-I途径上调，并且Sm失调的干扰素信号转导部分逆转。这些发现表明，Sm 疗法可能通过解除 IFN-I 途径的抑制来降低感染 Sm 感染的女性的 HIV 易感性。
Schistosoma mansoni(Sm) infection has been linked with an increased risk of HIV acquisition in women. Therefore, defining the mechanism(s) by whichSmalters HIV susceptibility might lead to new HIV prevention strategies. Here, we analyze the impact of standardSmtherapy in HIV-uninfectedSm+ Ugandan adult women on genital HIV susceptibility and mucosal and systemic immunology. Schistosomiasis treatment induces a profound reduction of HIV entry into cervical and blood CD4+ T cells that is sustained for up to two months, despite transient systemic and mucosal immune activation and elevated genital IL-1α levels. Genital IFN-α2a levels are also elevated post-treatment, and IFN-α2a blocks HIV entry into primary CD4+ T cells ex vivo. Transcriptomic analysis of blood mononuclear cells post-Smtreatment shows IFN-I pathway up-regulation and partial reversal ofSm-dysregulated interferon signaling. These findings indicate thatSmtherapy may reduce HIV susceptibility for women withSminfection, potentially through de-repression of IFN-I pathways.