| dc.description.abstract | Background: Restoration of the immune system has been observed in many cohorts worldwide upon initiation of antiretroviral therapy. However, we have reported partial restoration of the T cell subset function despite seven years of ART. We hypothesized that Innate immune functions among long term ART-treated HIV infected adults remain inferior to those of their age-matched HIV negative counterparts and this could negatively affect adaptive immune responses.
Methods: In a cross-sectional study, we compared NK cell, monocyte and ILC phenotypes and function among ART-treated adults with restored CD4 counts to ≥500 cells/µl, with age-matched HIV-negative individuals.
Using flow cytometry, we determined the subsets of NK cells (CD56dim and CD56bright), receptor expression (NKP44, NKP46 and NKG2D), immune activation (CD69, HLA-DR) and NK cell function (Granzyme B, CD107a and IFN-g). Monocyte subsets and function were determined including cytokine production (TNF, IL-6 and IL-1 beta) and antigen presentation ability (CD86 and CD40) upon stimulation with LPS. Microbial translocation (IFAB-P, LBP and LPS), monocyte activation (sCD14) and inflammation (IL-6 and D-dimer) were measured using ELISA. ILC subsets were determined by looking at the distribution of ILC1, ILC2 and ILC3 in peripheral blood. ILC function was determined by measuring the different amounts of cytokines each subset produced. [ILC1(IFN- γ), ILC2 (IL-4) and ILC3(IL- 17A)].
Data was analyzed using Flow jo 10.1 and Mann Whitney U tests were carried out for statistical analysis using Graph Pad Prism 6.
Results: Monocyte phenotypes and functions were significantly lower in HIV infected individuals than in HIV negative individuals: Non-classical monocytes (P=0.01), CD86 (P=0.0001), CD40 (P=0.02) and IL-1ß (P=0.01). Microbial translocation (IFAB-P, P=0.002), monocyte activation (sCD14, P=0.001) and inflammation (IL-6, P=0.04) were persistently higher in ART-treated HIV infected than among HIV negative individuals. NK cell phenotypes and functions were significantly lower in HIV infected individuals than among HIV negative individuals: CD56 dim (P=0.001), CD56 bright (p=0.05), Granzyme B production (P=0.005), CD107a expression (P=0.004), NKp46 (P=0.01) and NKG2D (P=0.0001). ILC3 cells were significantly lower among the HIV infected compared to HIV negative individuals (P=0.0001). ILC1 cells were significantly higher in HIV infected individuals compared to their age-matched HIV negative counterparts (P=0.009). The production of IFN- γ by ILC1 cells was significantly higher in the HIV infected individuals compared to their age-matched HIV negative counterparts (P=0.02).
Conclusions: We have described persistent perturbations in the monocyte, NK cell and ILC compartment. Further investigations are required to understand the drivers and potential remedies of abnormal innate immune functions to improve the recovery of both innate and adaptive immune functions during life-long ART. | en_US |
| dc.description.sponsorship | This work was supported through the DELTAS Africa Initiative [Grant# 107743/Z/15/Z], that funded Damalie Nakanjako and Rose Nabatanzi through a group leader award. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [Grant #107743/Z/15/Z] and the UK government.
he authors also acknowledge funding from the Alliance for Global Health and Science at the University of California, Berkeley, USA and the Wheeler Center for Emerging and Neglected Diseases, University of California, Berkeley, USA that funded our research to further understand Natural Killer cells and Innate immune cells during ART. | en_US |
