Biology subjects

Pereira Ribeiro, S.

Publications and source records attributed to Pereira Ribeiro, S..

3 recordsLinked to original sources

bioRxiv2026

Chronic opioid-associated immune dysregulation among people living with HIV

Objectives: Persistent immune dysregulation contributes to chronic disease among people living with HIV (PWH), even after viral suppression with antiretroviral therapy (ART). Although chronic opioid exposure is associated with adverse clinical outcomes, its impact on immune homeostasis during ART remains incompletely understood. We investigated whether opioid use disorder (OUD) is associated with persistent systemic and cellular immune dysregulation despite ART-mediated reductions in HIV viral load (VL). Methods: Peripheral blood was collected longitudinally from PWH with OUD (PWH/OUD+) and detectable HIV VL during 6 months of optimized ART (months 0, 3, and 6). A reference cohort of PWH without OUD (PWH/OUD-) and suppressed HIV VL provided a single blood sample. Immune profiling included plasma inflammatory biomarkers, multiplex cytokine analyses, spectral flow cytometry, and assessment of monocyte cytokine responses following lipopolysaccharide (LPS) stimulation. Mixed-effects models adjusted for HIV VL and VL-stratified analyses were performed. Results: PWH/OUD+ exhibited persistent immune dysregulation despite reductions in HIV VL. Plasma sCD163, sCD14, fractalkine, and I-TAC remained elevated, whereas TGF-{beta}1 was reduced. OUD was associated with expansion of CD16 monocytes and altered expression of CCR2, CD38, and CD11b. CD4 and CD8 T cells, NK cells, and B cells also exhibited persistent alterations in markers of activation, metabolism, and trafficking. Monocytes from PWH/OUD+ displayed attenuated cytokine responses following LPS stimulation. Conclusions: OUD is associated with persistent systemic and cellular immune dysfunction in PWH despite ART-mediated viral suppression, supporting opioid exposure as an independent contributor to chronic immune dysregulation that may promote inflammation, immune dysfunction, and long-term HIV-associated comorbidities. Keywords: HIV, Opioid-use disorder, innate immunity, cytokine

immunology↗

bioRxiv2021

IL-10 driven memory T cell survival and Tfh differentiation promote HIV persistence

Mechanisms regulating HIV persistence are complex and not well understood. Increased IL-10 levels were positively associated with HIV reservoir in blood and lymph nodes (LN) of treated HIV aviremic individuals. In LNs, B cells, regulatory T cells, follicular T helper cells (Tfh), monocytes and macrophages contributed to the frequencies of IL10+ cells. Cells with HIV DNA in LNs were in close proximity to IL-10+ cells and/or had the active form of STAT3, the transcription downstream of IL-10. Gene signatures and proteins associated to cell survival, Co-inhibitory receptors expression, maintenance of memory T cells, immune metabolism and Tfh frequencies were all modulated by IL-10 and associated with HIV reservoir persistence. In vitro, STAT3 knockout or neutralization of IL-10, reverted all the aforementioned pathways and resulted in 10-fold decay in HIV reservoir. Collectively, these results provide strong evidence for a pivotal role of IL-10 in HIV persistence, and a potential therapeutic strategy for HIV cure.

immunology↗

bioRxiv2018

Age but not disease progression defines CD4+ and CD8+ T stem cell memory levels in human retroviral infections: contrasting effects of HTLV-1 and HIV-1

BackgroundHuman CD4+ and CD8+ stem cell memory T cells (TSCM) represent a minor fraction of circulating lymphocytes characterized by stemness and long-term in vivo persistence. CD4+ TSCM are preferentially infected and constitute a reservoir for HIV-1, whereas CD8+ TSCM appear to play a protective role. However, little is known about CD4+ and CD8+ TSCM in the only other human pathogenic retroviral infection, human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 is the etiological agent of both Adult T-cell Leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraperesis (HAM/TSP), a neuroinflammatory disorder. In ATL, CD4+ TSCM cells were identified as the hierarchical leukemic stem cell, but data in HAM/TSP are lacking. Age is a major risk factor for both ATL and HAM/TSP, as both diseases generally manifest several decades after infection. Therefore, we explored a possible link between TSCM, age and disease status in human retroviral infections in a cross-sectional study, using multiparametric flow cytometry.\n\nResultsWe found that CD4+ or CD8+ TSCM levels (quantified as CD3+CD45RA+CD45RO- CD27+CCR7+Fashi) do not differ between healthy controls and untreated HTLV-1 infected individuals with and without neuroinflammatory disorder. However, we found both TSCM as well as CD8+ TSCM significantly accumulated with age, resulting in a >400% increase in elderly HTLV-1 infected individuals (>60 years). A significant correlation between age and TSCM signature genes was validated at the transcriptome level in an independent cohort. CD8+ but not CD4+ TSCM were significantly decreased in untreated HIV-1 infection. Unexpectedly, CD8+ TSCM recovery upon successful antiretroviral treatment was essentially complete (92.2{+/-}11.0%) in younger (<45 years) individuals, but significantly lower (37.3{+/-}6.1%) in older (>45 years) individuals (p=0.0003).\n\nConclusionIn HTLV-1 infection, an age-dependent accumulation of CD4+ and CD8+ TSCM points towards a possible protective role of CD8 TSCM in the elderly against leukemic but not neuroinflammatory disease. HIV-1-infected individuals lose their ability to restore CD8+ TSCM levels upon successful antiretroviral therapy at later age (>45 years), which might eventually lead to immunological failure and decreased vaccine efficacy.

immunology↗