Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Facultad de Medicina, Universidad de Alcalá, Instituto de Investigación Sanitaria Ramón y Cajal, Madrid, Spain.
Institute of Catalysis, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
J Infect Dis. 2021 Feb 13;223(3):471-481. doi: 10.1093/infdis/jiaa379.
Human immunodeficiency virus (HIV) infection impairs mucosal immunity and leads to bacterial translocation, fueling chronic inflammation and disease progression. While this is well established, questions remain about the compositional profile of the translocated bacteria, and to what extent it is influenced by antiretroviral therapy (ART). Using 16S ribosomal DNA targeted sequencing and shotgun proteomics, we showed that HIV increases bacterial translocation from the gut to the blood. HIV increased alpha diversity in the blood, which was dominated by aerobic bacteria belonging to Micrococcaceae (Actinobacteria) and Pseudomonadaceae (Proteobacteria) families, and the number of circulating bacterial proteins was also increased. Forty-eight weeks of ART attenuated this phenomenon. We found that enrichment with Lactobacillales order, and depletion of Actinobacteria class and Moraxellaceae and Corynebacteriacae families, were significantly associated with greater immune recovery and correlated with several inflammatory markers. Our findings suggest that the molecular cross talk between the host and the translocated bacterial products could influence ART-mediated immune recovery.
人类免疫缺陷病毒(HIV)感染会损害黏膜免疫,导致细菌易位,从而引发慢性炎症和疾病进展。虽然这一点已经得到充分证实,但仍存在一些问题,例如易位细菌的组成谱,以及它在多大程度上受抗逆转录病毒疗法(ART)的影响。我们使用 16S 核糖体 DNA 靶向测序和鸟枪法蛋白质组学技术,发现 HIV 会增加肠道到血液的细菌易位。HIV 增加了血液中的 alpha 多样性,其中优势菌群为微球菌科(放线菌)和假单胞菌科(变形菌),循环细菌蛋白的数量也增加了。48 周的 ART 治疗可减轻这种现象。我们发现,乳杆菌目(Lactobacillales order)的富集和放线菌纲(Actinobacteria)以及莫拉氏菌科(Moraxellaceae)和棒状杆菌科(Corynebacteriacae)的消耗与更大的免疫恢复显著相关,并与几种炎症标志物相关。我们的研究结果表明,宿主与易位细菌产物之间的分子相互作用可能会影响 ART 介导的免疫恢复。