PLOS子刊:HIV、精液微生物组和免疫反应的关联

摘要 : 美国翻译基因组学研究院(TGen)在新研究中,首次表明,HIV、精液中的细菌和免疫反应可能是有关联的。相关文章发表于2014年7月24日的《PLOS Pathogens》杂志上。

目前,医生通过基于HIV阳性男性血液中的病毒载量,来检测他们传染别人的可能性。然而,有些男性虽然血液中的病毒载量很低,但其精液中会产生大量的病毒。研究人员称这种现象为“区域化作用(compartmentalization)”——不同水平的病毒存在于人体的不同部位,例如精液和血液中。

不论在同性恋还是异性恋人群中,精液在HIV传播过程中都发挥重要的作用,因此,研究人员试图了解HIV如何被局域化在精液中。

在本研究中,美国翻译基因组学研究院(TGen)主要针对男同性恋,因为他们仍然是HIV感染风险最高的人群。这项研究包括27名感染HIV的男同性恋者,和22名未感染的男同性恋者。在对27名感染者进行抗逆转录病毒疗法前后的1个月和6个月间隔,对他们进行检测。来自22名未感染者的样本作为对照。

通过比较感染者和未感染者的精液细菌,研究人员发现,HIV会导致精液微生物组失调。这种失调可以通过HIV治疗得以纠正。这表明,在精液中存在复杂的宿主-微生物相互作用。他们还发现,较高水平的HIV,与较高水平的细菌和细胞因子(被描述为免疫系统警钟的生化物质)之间存在一种关联。

这项研究首次表明,HIV、精液中的细菌和免疫反应可能是有关联的。令研究人员特别兴奋的是,本研究可能对另外一个重要的患者人群很有意义。除了本研究的对象外,那些正接受治疗、但精液中有高水平HIV的男性。这对于改善我们如何治疗患者和控制HIV传播,非常的重要。

原文摘要:

The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV Infection

Cindy M. Liu, Brendan J. W. Osborne, Bruce A. Hungate, Kamnoosh Shahabi, Sanja Huibner, Richard Lester, Michael G. Dwan, Colin Kovacs,Tania L. Contente-Cuomo, Erika Benko, Maliha Aziz, Lance B. PrICE, Rupert Kaul

Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL) only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM), including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART) using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus,Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men,Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024), TNF-α (p = 0.009), and IL-1b (p = 0.002). IL-1b in particular was associated with semen VL (r2 = 0.18, p = 0.02). Semen bacterial load was also directly linked to the semen HIV VL (r2 = 0.15, p = 0.02). HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission.

作者:生物帮

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