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Influence of gut microbiome on mucosal immune activation and SHIV viral transmission in naive macaques.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2018-07-01 , DOI: 10.1038/s41385-018-0029-0
Yongjun Sui 1 , Amiran Dzutsev 2 , David Venzon 3 , Blake Frey 1 , Vishal Thovarai 2 , Giorgio Trinchieri 2 , Jay A Berzofsky 1
Affiliation  

It is unknown whether the gut microbiome affects HIV transmission. In our recent SHIV vaccine study, we found that the naive rhesus macaques from two different sources had significantly different rates of infection against repeated low-dose intrarectal challenge with SHIVSF162P4 virus. Exploring causes, we found that the more susceptible group of seven macaques had significantly more activated CD4+CCR5+Ki67+ T cells in the rectal mucosa than the more resistant group of 11 macaques from a different source. The prevalence of pre-challenge activated rectal CD4 T cells in the naive macaques correlated inversely with the number of challenges required to infect. Because the two naive groups came from different sources, we hypothesized that their microbiomes may differ and might explain the activation difference. Indeed, after sequencing 16s rRNA, we found differences between the two naive groups that correlated with immune activation status. Distinct gut microbiota induced different levels of immune activation ex vivo. Significantly lower ratios of Bacteroides to Prevotella, and significantly lower levels of Firmicutes were found in the susceptible cohort, which were also inversely correlated with high levels of immune activation in the rectal mucosa. Thus, host-microbiome interactions might influence HIV/SIV mucosal transmission through effects on mucosal immune activation.

中文翻译:

肠道微生物组对幼稚猕猴粘膜免疫激活和 SHIV 病毒传播的影响。

肠道微生物组是否影响 HIV 传播尚不清楚。在我们最近的 SHIV 疫苗研究中,我们发现来自两个不同来源的幼稚恒河猴对 SHIV SF162P4病毒的反复低剂量直肠内攻击具有显着不同的感染率。探索原因,我们发现更易感的七只猕猴组具有明显更多的激活 CD4 + CCR5 + Ki67 +直肠粘膜中的 T 细胞比来自不同来源的 11 只猕猴组更具抵抗力。幼稚猕猴中攻击前激活的直肠 CD4 T 细胞的流行与感染所需的攻击次数成反比。因为这两个天真的群体来自不同的来源,我们假设他们的微生物组可能不同并且可能解释激活差异。事实上,在对 16s rRNA 进行测序后,我们发现两个初始组之间的差异与免疫激活状态相关。不同的肠道微生物群在体外诱导不同水平的免疫激活。在易感人群中发现拟杆菌与普氏菌的比例显着降低,厚壁菌门的水平显着降低,这也与直肠粘膜中高水平的免疫激活呈负相关。因此,
更新日期:2018-06-02
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