Abstract
BackgroundThe influence of tobacco smoking on the immune system of HIV infected individuals is largely unknown. We investigated the impact of tobacco smoking on immune activation, microbial translocation, immune exhaustion and T-cell function in HIV infected individuals.MethodHIV infected smokers and non-smokers (n = 25 each) with documented viral suppression on combination antiretroviral therapy and HIV uninfected smokers and non-smokers (n = 15 each) were enrolled. Markers of immune activation (CD38 and HLA-DR) and immune exhaustion (PD1, Tim3 and CTLA4) were analyzed in peripheral blood mononuclear cells (PBMCs) by flow cytometry. Plasma markers of microbial translocation (soluble-CD14 - sCD14 and lipopolysaccharide - LPS) were measured. Antigen specific functions of CD4+ and CD8+ T-cells were measured, by flow cytometry, in PBMCs after 6 hours stimulation with Cytomegalovirus, Epstein-Barr virus and Influenza Virus (CEF) peptide pool.ResultsCompared to non-smokers, smokers of HIV infected and uninfected groups showed significantly higher CD4+ and CD8+ T-cell activation with increased frequencies of CD38+HLA-DR+ cells with a higher magnitude in HIV infected smokers. Expressions of immune exhaustion markers (PD1, Tim3 and CTLA4) either alone or in combinations were significantly higher in smokers, especially on CD4+ T-cells. Compared to HIV uninfected non-smokers, microbial translocation (sCD14 and LPS) was higher in smokers of both groups and directly correlated with CD4+ and CD8+ T-cell activation. Antigen specific T-cell function showed significantly lower cytokine response of CD4+ and CD8+ T-cells to CEF peptide-pool stimulation in smokers of both HIV infected and uninfected groups.ConclusionsOur results suggest that smoking and HIV infection independently influence T-cell immune activation and function and together they present the worst immune profile. Since smoking is widespread among HIV infected individuals, studies are warranted to further evaluate the cumulative effect of smoking on impairment of the immune system and accelerated disease progression.
Highlights
The prevalence of tobacco smoking among people living with HIV is as high as 70% [1]
Expressions of immune exhaustion markers (PD1, T-cell Ig domain and mucin domain-3 (Tim3) and Cytotoxic T-Lymphocyte Antigen-4 (CTLA4)) either alone or in combinations were significantly higher in smokers, especially on CD4+ T-cells
Our results suggest that smoking and HIV infection independently influence T-cell immune activation and function and together they present the worst immune profile
Summary
The prevalence of tobacco smoking among people living with HIV is as high as 70% [1]. Evidence indicates that despite years of successful treatment, immune activation (IA) and markers of inflammation remain abnormally high during HIV infection [2]. These findings are concerning given that IA has proven a better predictor of disease progression than plasma viral load (VL) [3]. During the course of HIV infection, T-cell functions such as proliferation and cytotoxic potential appear to diminish gradually leading to an incremental progression toward immune exhaustion (IE) [8]. We investigated the impact of tobacco smoking on immune activation, microbial translocation, immune exhaustion and T-cell function in HIV infected individuals
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