Abstract
HIV-1 increases susceptibility to pulmonary infection and disease, suggesting pathogenesis in the lung. However, the lung immune environment during HIV infection remains poorly characterized. This study examined T cell activation and the cytokine milieu in paired bronchoalveolar lavage (BAL) and blood from 36 HIV-uninfected and 32 HIV-infected participants. Concentrations of 27 cytokines were measured by Luminex, and T cells were phenotyped by flow cytometry. Blood and BAL had distinct cytokine profiles (p=0.001). In plasma, concentrations of inflammatory cytokines like IFN-γ (p=0.004) and TNF-α (p=0.004) were elevated during HIV infection, as expected. Conversely, BAL cytokine concentrations were similar in HIV-infected and uninfected individuals, despite high BAL viral loads (VL; median 48,000 copies/ml epithelial lining fluid). HIV-infected individuals had greater numbers of T cells in BAL compared to uninfected individuals (p=0.007); and BAL VL positively associated with CD4+ and CD8+ T cell numbers (p=0.006 and p=0.0002, respectively) and CXCL10 concentrations (p=0.02). BAL T cells were highly activated in HIV-infected individuals, with nearly 2-3 fold greater frequencies of CD4+CD38+ (1.8-fold; p=0.007), CD4+CD38+HLA-DR+ (1.9-fold; p=0.0006), CD8+CD38+ (2.8-fold; p=0.0006), CD8+HLA-DR+ (2-fold; p=0.022) and CD8+CD38+HLA-DR+ (3.6-fold; p<0.0001) cells compared to HIV-uninfected individuals. Overall, this study demonstrates a clear disruption of the pulmonary immune environment during HIV infection, with readily detectable virus and activated T lymphocytes, which may be driven to accumulate by local chemokines.
Highlights
Sub-Saharan Africa has 25.6 million people currently living with HIV and 970,000 new infections a year [1]
As reported previously [29], we found that the absolute numbers of T cells from bronchoalveolar lavage (BAL) were significantly higher in HIV-infected participants, and this correlated positively with BAL viral load (Figure S1)
We found distinct compartmentalisation of cytokines between BAL and blood in terms of relative cytokine abundance and cytokine concentrations, regardless of HIV status, leading us to examine the effect of HIV on each compartment individually
Summary
Sub-Saharan Africa has 25.6 million people currently living with HIV and 970,000 new infections a year [1]. Antiretroviral treatment (ART) has reduced the overall prevalence of HIVassociated lung disease, respiratory diseases still contribute to substantial morbidity and mortality in the HIV-infected population [5,6,7]. This suggests that HIV pathogenesis extends to the lungs, requiring additional strategies to reduce the burden of respiratory diseases in HIV-infected individuals. HIV infection is characterized by systemic immune hyperactivation and profound damage to mucosal compartments due to viral replication [8,9,10,11,12,13,14,15,16]. In this study, we examined viral burden, T cell activation and cytokine concentrations in paired BAL and blood from HIV-uninfected and HIV-infected participants
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
