Alcohol abuse is prevalent in HIV infected patients and is associated with suboptimal responses to antiretroviral therapy (ART). Both HIV and alcohol abuse predispose to infections at mucosal sites of which bacterial pneumonia is a common complication. During the last funding period, we found that experimental pneumonia using Streptococcus pneumoniae in alcohol fed, SIV-infected macaques resulted in statistically significant higher viral loads in the lung. This may be due to increased virus production by prolonged activation of cells (either CD4+ macrophages or CD4+ T-cells) and/or due to reduced SIV-specific cytotoxic CD8+ T-cells. Our lab has also demonstrated that IL-17 and IL-22, products of a subset of CD4+ T-cells, Th17 cells, play critical roles in mucosal immunity against extracellular bacterial infections in the lung. SIV infection leads to a loss of mucosal IL-17 producing T-cells and reduces expression of mucosal IL-17 and IL-22 resulting in Impaired local bacterial control in the intestine. Whether a similar depletion of Th17 cells occurs in the lung is unknown. Furthermore, preliminary studies show that alcohol suppresses IL-17 production by murine and non-human primate T-cells in vitro. These data suggest that alcohol and HIV/SIV may have additive or synergistic effects on mucosal T-cell populations and immunity in the lung. Additionally alcohol may impair T-cell reconstitution during ART. These data lead us to hypothesize that chronic alcohol ingestion is additive or synergistic with SIV to impair CD4+ Th-cell immune responses to extracellular pathogens. Utilizing our well-characterized model of intragastric ethanol feeding in the SIV rhesus macaque model, our Specific Aims are to: 1) Test the prediction that alcohol consumption will impair recovery of peripheral CD4+ T cells during ART treatment for SIV infection;2) Test the prediction that chronic alcohol consumption will impair the mucosal IL-17 and IL-22 responses to experimental pneumonia with S. pneumoniae as well as the generation of memory CD4+ T-cells after bacterial challenge. These experiments will improve our understanding on the respective roles of SIV, alcohol and the response to ART in terms of pulmonary mucosal immunity.

Public Health Relevance

Alcohol and HIV are significant co-factors that predispose to infection. This project will investigate if alcohol and SIV (a model of HIV) depletes specific types of T helper cells which may explain in part the increased risk of opportunistic infections. This knowledge will not only advance our understanding of disease pathogenesis but also identify immune effector arms that can be the subject of future vaccine strategies to prevent infectious complications of HIV/AIDS.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
5P60AA009803-21
Application #
8577102
Study Section
Special Emphasis Panel (ZAA1-DD)
Project Start
Project End
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
21
Fiscal Year
2014
Total Cost
$115,580
Indirect Cost
$34,256
Name
Louisiana State Univ Hsc New Orleans
Department
Type
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Samuelson, Derrick R; Burnham, Ellen L; Maffei, Vincent J et al. (2018) The respiratory tract microbial biogeography in alcohol use disorder. Am J Physiol Lung Cell Mol Physiol 314:L107-L117
Glick, Jennifer L; Theall, Katherine P; Andrinopoulos, Katherine M et al. (2018) The Role of Discrimination in Care Postponement Among Trans-Feminine Individuals in the U.S. National Transgender Discrimination Survey. LGBT Health 5:171-179
Molina, Patricia E; Nelson, Steve (2018) Binge Drinking's Effects on the Body. Alcohol Res 39:99-109
Molina, Patricia E; Simon, Liz; Amedee, Angela M et al. (2018) Impact of Alcohol on HIV Disease Pathogenesis, Comorbidities and Aging: Integrating Preclinical and Clinical Findings. Alcohol Alcohol 53:439-447
Ford Jr, Stephen M; Simon Peter, Liz; Berner, Paul et al. (2018) Differential contribution of chronic binge alcohol and antiretroviral therapy to metabolic dysregulation in SIV-infected male macaques. Am J Physiol Endocrinol Metab :
Boule, Lisbeth A; Ju, Cynthia; Agudelo, Marisela et al. (2018) Summary of the 2016 Alcohol and Immunology Research Interest Group (AIRIG) meeting. Alcohol 66:35-43
Glick, Jennifer L; Andrinopoulos, Katherine M; Theall, Katherine P et al. (2018) ""Tiptoeing Around the System"": Alternative Healthcare Navigation Among Gender Minorities in New Orleans. Transgend Health 3:118-126
Glick, Jennifer L; Theall, Katherine; Andrinopoulos, Katherine et al. (2018) For data's sake: dilemmas in the measurement of gender minorities. Cult Health Sex :1-16
Theall, Katherine P; Felker-Kantor, Erica; Wallace, Maeve et al. (2018) Considering high alcohol and violence neighborhood context using daily diaries and GPS: A pilot study among people living with HIV. Drug Alcohol Depend 187:236-241
Simon, Liz; Siggins, Robert; Winsauer, Peter et al. (2018) Simian Immunodeficiency Virus Infection Increases Blood Ethanol Concentration Duration After Both Acute and Chronic Administration. AIDS Res Hum Retroviruses 34:178-184

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