Microbial Effects on Immunity in HIV: Virus, Gender or Sexual Preference Induced?
Microbial Effects on Immunity in HIV: Virus, Gender or Sexual Preference Induced?
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微生物对艾滋病毒免疫的影响：引起病毒，性别或性偏爱？
DOI：
10.1016/j.ebiom.2018.04.008
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发表时间：
2018-05
期刊：
影响因子：
11.1
通讯作者：
Manuzak JA
中科院分区：
文献类型：
--
作者：
Klatt NR;Manuzak JA
在HIV感染的背景下已经深入研究了肠道微生物菌群，因为微生物组组成的改变或微生物生态失调可能影响粘膜功能障碍和屏障破坏，导致细菌移位到全身外周的增加（Zevin et al.，2016）。这反过来又可能有助于增加全身免疫激活，这与未经治疗的个体的HIV疾病进展以及抗逆转录病毒疗法（ART）治疗的HIV感染个体的发病率和死亡率增加有关。旨在表征HIV感染者肠道微生物组组成的初步研究表明，与未感染者相比，细菌群落结构发生了变化。特别地，在HIV感染的个体中，诸如普雷沃氏菌属（Prevotella）和不动杆菌属（Acinetobacter）以及变形菌门（Proteobacteria）的属的相对丰度显示出增加，并且这些增加的丰度与粘膜和全身免疫活化和微生物易位的频率升高相关（Dillon等人，2014; Dillon等人，2015）。相比之下，健康的肠道如厚壁菌门和拟杆菌在HIV感染中减少，可能导致粘膜健康的丧失。更重要的是，最近的数据表明，以前归因于艾滋病毒感染的微生物变化实际上可能与性取向有关。事实上，与男性发生性关系的血清阴性男性（MSM）显示出富含普雷沃氏菌属的微生物组，与HIV感染无关（Kelley et al.，2016年，Noguera-Julian等人，2016年）。这些发现强调了更好地了解微生物组如何受到疾病和生活方式影响的重要性，并确定了微生物群落作为一个整体的改变可能导致艾滋病毒感染的全身炎症特征加剧的确切机制。在这一期的EBioMedicine中，Neff et al.（2018）解决了整个微生物群落如何影响HIV感染背景下的炎症和免疫激活的问题。在此，不是如先前所做的那样用已显示为微生态失调的单个细菌物种刺激（Dillon等人，2015; Lozupone等人，2013年），作者开发了一种方法，通过该方法可以从代表性个体的粪便中分离出整个粪便细菌群落（FBCs）。重要的是，作者从许多不同的群体中分离出FBCs，包括（1）ART初治的HIV感染的MSM，（2）ART经历的HIV感染的MSM，（3）HIV未感染的MSM，（4）HIV未感染的异性恋男性，（5）ART经历的HIV感染的女性，和（6）HIV未感染的女性，共同努力考虑生物学和生活方式因素，包括性偏好，抗逆转录病毒治疗和性别。使用这种方法，作者证明，与来自HIV感染和血清阴性MSM的FBC培养的外周血单核细胞（PBMC）相比，与来自血清阴性异性恋男性的FBC培养的PBMC具有更大的单核细胞活化。此外，与血清阴性MSM相比，来自未经治疗的HIV感染的MSM的FBC诱导更大的促炎细胞因子产生和CD 4 + T细胞活化。类似地，与血清阴性女性的FBCs相比，在用HIV感染的ART治疗女性的FBCs刺激的PBMC中观察到升高的CD 4 + T细胞活化和炎性细胞因子产生。最后，升高的T细胞活化被证明是由单核细胞介导的，这主要是由FBCs通过Toll样受体（TLRs）诱导的。
The intestinal microflora has been intensely studied in the context of HIV infection, as alterations in the composition of the microbiome, or microbial dysbiosis, could impact mucosal dysfunction and barrier breakdown, leading to elevated translocation of bacteria into the systemic periphery (Zevin et al., 2016). This in turn could contribute to increased systemic immune activation, which has been associated with enhanced HIV disease progression in untreated individuals, and morbidity and mortality in antiretroviral therapy (ART)-treated, HIV-infected individuals. Initial studies designed to characterize the composition of the intestinal microbiome in HIV-infected individuals demonstrated that bacterial community structure was altered as compared to uninfected individuals. In particular, the relative abundance of genera such as Prevotella and Acinetobacter as well as the phylum Proteobacteria, were shown to be increased in HIV-infected individuals and these increased abundances were associated with elevated frequencies of mucosal and systemic immune activation and microbial translocation (Dillon et al., 2014; Dillon et al., 2015). In contrast, healthy commensals such as Firmicutes and Bacteroides were decreased in HIV infection, potentially contributing to loss of mucosal health. Critically, more recent data has demonstrated that the microbial alterations previously ascribed to HIV infection may in fact be linked to sexual preference. Indeed, seronegative men who have sex with men (MSM) were shown to exhibit microbiomes rich in Prevotella, independent of HIV infection (Kelley et al., 2016, Noguera-Julian et al., 2016). These findings highlight the importance of developing a better understanding of how the microbiome is impacted by disease as well as lifestyle and of defining the exact mechanisms by which alterations in microbial communities as a whole, could contribute to the exacerbated systemic inflammation characteristic of HIV-infection. In this issue of EBioMedicine, Neff et al.(2018) addressed the question of how entire microbial communities may impact inflammation and immune activation in the context of HIV infection. Here, rather than stimulating with individual bacterial species that have been shown to be dysbiotic as has been done previously (Dillon et al., 2015; Lozupone et al., 2013), the authors developed a method by which whole fecal bacterial communities (FBCs) could be isolated from the stool of representative individuals. Importantly, the authors isolated FBCs from a number of different groups, including (1) ART-naïve HIV-infected MSM,(2) ART-experienced HIV-infected MSM,(3) HIV-uninfected MSM,(4) HIV-uninfected heterosexual males,(5) ART-experienced HIV-infected females, and (6) HIV-uninfected females, in a concerted effort to take into account biological and lifestyle factors including sexual preference, ART treatment and gender. Using this method, the authors demonstrate that peripheral blood mononuclear cells (PBMCs) cultured with FBCs from HIV-infected and seronegative MSM had greater monocyte activation as compared to PBMCs cultured with FBCs from seronegative heterosexual males. In addition, FBC from untreated HIV-infected MSM induced greater pro-inflammatory cytokine production and CD4+ T cell activation as compared to seronegative MSM. Similarly, elevated CD4+ T cell activation and inflammatory cytokine production was observed in PBMC stimulated with FBCs from HIV-infected, ART-treated females, as compared to FBCs from seronegative females. Finally, elevated T cell activation was shown to be mediated by monocytes, which were induced by FBCs mainly through Toll-like receptors (TLRs …
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影响因子：
11.1
作者：
Noguera-Julian M;Rocafort M;Guillén Y;Rivera J;Casadellà M;Nowak P;Hildebrand F;Zeller G;Parera M;Bellido R;Rodríguez C;Carrillo J;Mothe B;Coll J;Bravo I;Estany C;Herrero C;Saz J;Sirera G;Torrela A;Navarro J;Crespo M;Brander C;Negredo E;Blanco J;Guarner F;Calle ML;Bork P;Sönnerborg A;Clotet B;Paredes R
通讯作者：
Paredes R
影响因子：
5.4
作者：
Hensley-McBain, Tiffany;Zevin, Alexander S.;Klatt, Nichole R.
通讯作者：
Klatt, Nichole R.
影响因子：
12.2
作者：
Vujkovic-Cvijin, Ivan;Rutishauser, Rachel L.;Somsouk, Ma
通讯作者：
Somsouk, Ma
影响因子：
8
作者：
Kelley CF;Kraft CS;de Man TJ;Duphare C;Lee HW;Yang J;Easley KA;Tharp GK;Mulligan MJ;Sullivan PS;Bosinger SE;Amara RR
通讯作者：
Amara RR
影响因子：
2.1
作者：
Zevin, Alexander S.;Hensley-McBain, Tiffany;Klatt, Nichole R.
通讯作者：
Klatt, Nichole R.