Alcohol consumption increases susceptibility to pneumococcal pneumonia in a humanized murine HIV model mediated by intestinal dysbiosis.
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 mechanis...
| Publicado en: | Alcohol Vol. 80; pp. 33 - 44 |
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| Autores principales: | , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Elsevier B.V.
Nov2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=139295708&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 139295708 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 07418329 J8J jtl: Alcohol issn: 07418329 maglogo: N pubinfo: dt: Nov2019 vid: 80 pid: 82545 pub: Elsevier B.V. place: Philadelphia, Pennsylvania artinfo: ui: 139295708 139295708 NLM30213614 10.1016/j.alcohol.2018.08.012 NLM30213614 139295708 ppf: 33 ppct: 11 formats: tig: atl: Alcohol consumption increases susceptibility to pneumococcal pneumonia in a humanized murine HIV model mediated by intestinal dysbiosis. aug: au: Samuelson, Derrick R. Siggins, Robert W. Ruan, Sanbao Amedee, Angela M. Sun, Jiusong Zhu, Quan Karen Marasco, Wayne A. Taylor, Christopher M. Luo, Meng Welsh, David A. Shellito, Judd E. affil: Department of Internal Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA, United States sug: subj: HIV Infections Complications Disease Susceptibility Chemically Induced Pathologic Processes Microbiology Pneumonia, Bacterial Etiology Ethanol Adverse Effects Models, Biological Disease Susceptibility Microbiology Hematopoietic Stem Cell Transplantation Liver Transplantation Pathologic Processes Xenografts Viral Load Thymus Gland Transplantation Bone Marrow Transplantation Disease Susceptibility CD4 Lymphocyte Count Animals Female RNA Mice Female ab: 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 × 104 TCID50 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 × 105 CFU (colony-forming units) of S. pneumoniae and were sacrificed 48 h later. HIV-infected mice had viral loads of ∼2 × 104 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. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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