Department of Internal Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA, United States.
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, United States.
Alcohol. 2019 Nov;80:33-43. doi: 10.1016/j.alcohol.2018.08.012. Epub 2018 Sep 11.
Alcohol use in persons living with HIV (PLWH) worsens the severity of bacterial pneumonia. However, the exact mechanism(s) by which this occurs remain ill-defined. We hypothesized that alcohol in the setting of HIV infection decreases Streptococcus pneumoniae clearance from the lung through mechanisms mediated by the gut microbiota. Humanized BLT (bone marrow, liver, thymus) mice were infected with 1 × 10 TCID of HIV (BAL and JRCSF strains) via intraperitoneal (i.p.) injection. One week post-HIV infection, animals were switched to a Lieber-DeCarli 5% ethanol diet or an isocaloric control diet for 10 days. Alcohol-fed animals were also given two binges of 2 g/kg ethanol on days 5 and 10. Feces were also collected, banked, and the community structures were analyzed. Mice were then infected with 1 × 10 CFU (colony-forming units) of S. pneumoniae and were sacrificed 48 h later. HIV-infected mice had viral loads of ∼2 × 10 copies/mL of blood 1 week post-infection, and exhibited an ∼57% decrease in the number of circulating CD4+ T cells at the time of sacrifice. Fecal microbial community structure was significantly different in each of the feeding groups, as well as with HIV infection. Alcohol-fed mice had a significantly higher burden of S. pneumoniae 48 h post-infection, regardless of HIV status. In follow-up experiments, female C57BL/6 mice were treated with a cocktail of antibiotics daily for 2 weeks and recolonized by gavage with intestinal microbiota from HIV+ ethanol-fed, HIV+ pair-fed, HIV- ethanol-fed, or HIV- pair-fed mice. Recolonized mice were then infected with S. pneumoniae and were sacrificed 48 h later. The intestinal microbiota from alcohol-fed mice (regardless of HIV status) significantly impaired clearance of S. pneumoniae. Collectively, these data indicate that alcohol feeding, as well as alcohol-associated intestinal dysbiosis, compromise pulmonary host defenses against pneumococcal pneumonia. Determining whether HIV infection acts synergistically with alcohol use in impairing pulmonary host defenses will require additional study.
在感染 HIV 的人群（PLWH）中饮酒会使细菌性肺炎的严重程度恶化。然而，其具体机制仍未明确。我们假设，在 HIV 感染的情况下，酒精通过肠道微生物群介导的机制，减少了肺炎链球菌从肺部的清除。通过腹腔内（i.p.）注射，将人源化 BLT（骨髓、肝脏、胸腺）小鼠感染 1×10 TCID 的 HIV（BAL 和 JRCSF 株）。感染 HIV 1 周后，动物切换至 Lieber-DeCarli 5%乙醇饮食或等热量对照饮食 10 天。在第 5 天和第 10 天，酒精喂养的动物还给予两次 2g/kg 乙醇的 binge。还收集了粪便，储存起来，并分析了其群落结构。然后，将小鼠感染 1×10 CFU（集落形成单位）的肺炎链球菌，并在 48 小时后处死。感染 HIV 的小鼠在感染后 1 周血液中的病毒载量约为 2×10 拷贝/mL，在处死时循环 CD4+T 细胞的数量减少了约 57%。在每种喂养组中，以及在 HIV 感染时，粪便微生物群落结构都有显著差异。无论 HIV 状态如何，酒精喂养的小鼠在感染后 48 小时内肺炎链球菌的负担明显更高。在后续实验中，用抗生素鸡尾酒每天治疗雌性 C57BL/6 小鼠 2 周，并通过灌胃用来自 HIV+乙醇喂养、HIV+配对喂养、HIV-乙醇喂养或 HIV-配对喂养小鼠的肠道微生物群重新定植。重新定植的小鼠随后感染肺炎链球菌，并在 48 小时后处死。来自酒精喂养小鼠（无论 HIV 状态如何）的肠道微生物群显著损害了肺炎链球菌的清除。总的来说，这些数据表明，酒精喂养以及与酒精相关的肠道菌群失调，会损害肺部宿主对肺炎球菌性肺炎的防御能力。确定 HIV 感染是否与酒精使用协同作用，从而损害肺部宿主防御能力，还需要进一步研究。
