Innate lymphoid cell dysfunction during long-term suppressive antiretroviral therapy in an African cohort

Rose Nabatanzi,Moses Joloba,Damalie Nakanjako,Sarah Rowland Jones,Glenda Canderan,Stephen Cose,Lois Bayigga

doi:10.1186/s12865-021-00450-8

Abstract

BackgroundInnate lymphoid cells (ILC) are lymphoid lineage innate immune cells that do not mount antigen-specific responses due to their lack of B and T-cell receptors. ILCs are predominantly found at mucosal surfaces, as gatekeepers against invading infectious agents through rapid secretion of immune regulatory cytokines. HIV associated destruction of mucosal lymphoid tissue depletes ILCs, among other immune dysfunctions. Studies have described limited restoration of ILCs during the first three years of combined antiretroviral therapy (cART). Little is known about restoration of ILCs during long-term cART, particularly in sub-Saharan Africa which hosts increasing numbers of adults with at least a decade of cART.ResultsWe examined phenotypes and function of ILCs from peripheral blood mononuclear cells after 12 years of suppressive cART. We report that ILC1 frequencies (T-BET + CD127 + and CD161 +) were higher in cART-treated HIV-infected relative to age-matched health HIV-negative adults; P = 0.04 whereas ILC precursors (ILCP) were comparable in the two groups (P = 0.56). Interferon gamma (IFN-γ) secretion by ILC1 was higher among cART-treated HIV-infected relative to HIV-negative adults (P = 0.03).ConclusionHIV associated alteration of ILC persisted during cART and may likely affect the quality of host innate and adaptive immune responses during long-term cART.

Highlights

Innate lymphoid cells (ILCs), a relatively newly identified group of innate immune cells of lymphoid lineage without B or T-cell receptors [1], are predominantly found at barrier surfaces exposed to infectious agents including skin, lungs and intestinal mucosal surfaces [2]
Off the ILC precursors (ILCP) cells, T-BET + and CD161 + were gated as ILC1, CRTH2 +, CD161 + were gated as ILC2 and ROR-gt + cells were gated as ILC3 cells (Fig. 1)
ILCP percentages in peripheral blood mononuclear cells of combined antiretroviral therapy (cART)-treated HIVinfected adults were comparable to those found in age-matched healthy HIV-negative counterparts; p = 0.56 whereas ILC1 percentages were significantly higher in cART-treated HIV-infected adults [median 10.5, Interquartile range (IQR) (0.59, 58.0)], relative to age-matched healthy HIV-negative individuals [median 4.3, IQR (0.084, 20.00)], P = 0.04 whereas ILC3 percentages were lower in peripheral blood mononuclear cells of cART-treated HIV-infected adults [median 0.15, IQR (0.0,10.53)] relative to age-matched healthy HIV-negative counterparts [median 9.27, IQR (0.18,27.0)] P ≤ 0.0001] (Fig. 2)

Summary

Introduction

Innate lymphoid cells (ILCs), a relatively newly identified group of innate immune cells of lymphoid lineage without B or T-cell receptors [1], are predominantly found at barrier surfaces exposed to infectious agents including skin, lungs and intestinal mucosal surfaces [2]. CD4 T-helper cells; TH1, TH2, and TH17 respectively; through the specific transcription factors expressed and cytokines produced [3]. ILC are approximately 0.01–0.1% of cells in peripheral blood, their specialised ability to produce large amounts of cytokines and maintain homeostasis is critical [2, 9,10,11]. Innate lymphoid cells (ILC) are lymphoid lineage innate immune cells that do not mount antigen-specific responses due to their lack of B and T-cell receptors. ILCs are predominantly found at mucosal surfaces, as gatekeepers against invading infectious agents through rapid secretion of immune regulatory cytokines. Little is known about restoration of ILCs during long-term cART, in sub-Saharan Africa which hosts increasing numbers of adults with at least a decade of cART

Results

Discussion

Conclusion