The semen microbiome and its relationship with local immunology and viral load in HIV infection.
The semen microbiome and its relationship with local immunology and viral load in HIV infection.
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DOI：
10.1371/journal.ppat.1004262
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发表时间：
2014-07
期刊：
影响因子：
6.7
通讯作者：
Kaul R
中科院分区：
文献类型：
--
作者：
Liu CM;Osborne BJ;Hungate BA;Shahabi K;Huibner S;Lester R;Dwan MG;Kovacs C;Contente-Cuomo TL;Benko E;Aziz M;Price LB;Kaul R
精液是 HIV 传播的主要载体，但精液 HIV RNA 病毒载量 (VL) 与血液 VL 仅有中等相关性。生殖器感染和相关炎症可以增强病毒脱落，但在没有经典病原体的情况下也可能发生。因此，我们假设精液微生物组失调与局部艾滋病毒脱落有关。我们使用基于 16S rRNA 基因的焦磷酸测序和定量 PCR 在基线和开始抗逆转录病毒治疗 (ART) 后分析了 49 名男男性行为者 (MSM) 的精液样本，其中包括 22 名未感染 HIV 的男性和 27 名感染 HIV 的男性。我们通过线性回归、非度量多维尺度和拟合优度检验研究了精液细菌与 HIV 感染、精液细胞因子水平和精液 VL 的关系。无论艾滋病毒感染状况如何，链球菌、棒状杆菌和葡萄球菌都是常见的精液细菌。虽然解脲支原体是未感染艾滋病毒的男性中最丰富的软体动物，但支原体在艾滋病毒感染后占主导地位。 HIV 感染与精液微生物组多样性和丰富度下降有关，在 ART 六个月后恢复。在感染 HIV 的男性中，精液细菌载量与七种促炎精液细胞因子相关，包括 IL-6 (p = 0.024)、TNF-α (p = 0.009) 和 IL-1b (p = 0.002)。 IL-1b 尤其与精液 VL 相关（r2 = 0.18，p = 0.02）。精液细菌载量也与精液 HIV VL 直接相关（r2 = 0.15，p = 0.02）。 HIV 感染重塑了精液细菌和促炎细胞因子之间的关系，两者都与精液 VL 相关，这支持了精液微生物组在 HIV 性传播中的作用。 HIV 感染性的经典范例以血液 HIV RNA 病毒载量为中心。然而，虽然精液和脑脊液等其他液体室可能具有与血液不同的病毒载量，但局部艾滋病毒脱落的原因尚不完全清楚。由于精液病毒载量是 HIV 传播风险的独立预测因子，因此了解引发精液病毒脱落增加的局部因素至关重要，以便制定新的预防策略。在这里，我们评估了 22 名未感染 HIV 的男男性行为者 (MSM) 和 27 名感染 HIV 的 MSM 在开始抗逆转录病毒治疗 (ART) 前后的精液微生物组、细菌负荷和细胞因子水平。我们发现 HIV 感染会降低精液微生物组的生物多样性，而这种生物多样性可以通过 ART 和免疫重建来恢复。我们还发现，未经治疗的艾滋病毒感染男性精液细菌载量与七种精液细胞因子的水平相关，这种关系在未感染的对照中未见。特别是，细胞因子 IL-1b 与精液细菌和病毒载量具有独特的相关性。我们的研究结果支持精液微生物组与局部免疫学之间的相互作用，并表明 IL-1b 可能是精液微生物组触发精液病毒脱落的机制。
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. The classical paradigm of HIV infectivity centers on the blood HIV RNA viral load. However, while other fluid compartments such as semen and cerebrospinal fluid can have distinct viral loads from blood, the causes of localized HIV shedding are not fully understood. Since the semen viral load is an independent predictor of HIV transmission risk, it is critical to understand the local factors that trigger increased semen viral shedding in order to develop novel preventative strategies. Here, we evaluated the semen microbiome, bacterial load, and cytokine levels in 22 HIV-uninfected men who have sex with men (MSM) and in 27 HIV-infected MSM before and after initiation of antiretroviral therapy (ART). We found that HIV infection reduces semen microbiome biodiversity, which is restored with ART and immune reconstitution. We also found that semen bacterial load in untreated, HIV-infected men is associated with the levels of seven semen cytokines, relationships not seen in the uninfected controls. In particular, the cytokine IL-1b was uniquely correlated with both semen bacterial and viral load. Our findings support the interaction between semen microbiome and local immunology, and suggest that IL-1b could be a mechanism for semen microbiome to trigger semen viral shedding.
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影响因子：
6.4
作者：
Liu CM;Hungate BA;Tobian AA;Serwadda D;Ravel J;Lester R;Kigozi G;Aziz M;Galiwango RM;Nalugoda F;Contente-Cuomo TL;Wawer MJ;Keim P;Gray RH;Price LB
通讯作者：
Price LB
影响因子：
17.1
作者：
Baeten JM;Kahle E;Lingappa JR;Coombs RW;Delany-Moretlwe S;Nakku-Joloba E;Mugo NR;Wald A;Corey L;Donnell D;Campbell MS;Mullins JI;Celum C;Partners in Prevention HSV/HIV Transmission Study Team
通讯作者：
Partners in Prevention HSV/HIV Transmission Study Team
影响因子：
6.4
作者：
Coombs, RW;Speck, CE;Krieger, JN
通讯作者：
Krieger, JN
影响因子：
4.2
作者：
Liu CM;Kachur S;Dwan MG;Abraham AG;Aziz M;Hsueh PR;Huang YT;Busch JD;Lamit LJ;Gehring CA;Keim P;Price LB
通讯作者：
Price LB
影响因子：
3.4
作者：
Kaul, R.;Pettengell, C.;Rebbapragada, A.
通讯作者：
Rebbapragada, A.