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Alcohol. 2018 Sep 10. pii: S0741-8329(18)30166-6. doi: 10.1016/j.alcohol.2018.08.012. [Epub ahead of print]

Alcohol consumption increase susceptibility to pneumococcal pneumonia in a humanized murine HIV model mediated by intestinal dysbiosis.

Author information

1
Department of Internal Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
2
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
3
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
4
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School Boston, MA, USA.
5
Department of Internal Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA, USA; Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
6
Department of Internal Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA, USA; Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, USA. Electronic address: jshell@lsuhsc.edu.

Abstract

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 S. pneumoniae clearance from the lung through mechanisms mediated by the gut microbiota. Humanized BLT (bone marrow, liver, thymus) mice were infected with 1x104 TCID50 of HIV (BAL and JRCSF strains) via IP 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 2 binges of 2 g kg-1 ethanol on days 5 and 10. Feces were also collected, banked, and the community structures were analyzed. Mice were then infected with 1x105 CFU of S. pneumoniae and sacrificed 48 hours later. HIV-infected mice had viral loads of ∼2x104 copies/mL of blood one 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 hours post infection, regardless of HIV status. In follow-up experiments, female C57BL/6 mice were treated with a cocktail of antibiotics daily for two 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 sacrificed 48 hours 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 defense against pneumococcal pneumonia. Whether HIV infection acts synergistically with alcohol-use in impairing pulmonary host defense will require additional study.

KEYWORDS:

Alcohol; S. pnuemoniae; host-defense; microbiota; pulmonary

PMID:
30213614
PMCID:
PMC6449221
[Available on 2020-03-10]
DOI:
10.1016/j.alcohol.2018.08.012

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