{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T07:10:03Z","timestamp":1794035403514,"version":"4.8.0"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Elite controllers can spontaneously control HIV-1 infection without antiretroviral treatment but remain at risk of developing non-AIDS-related conditions. The adaptive immune system is key in mediating spontaneous viral control; however, the innate immune response remains understudied. We assessed the quality of the innate immune responses by evaluating the phenotype and function of antigen-presenting cells (APCs) in South African adults living with HIV (PWH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      A total of 73 black South Africans were included in this study. Of these, 55 were living with HIV and included 16 individuals with spontaneous viral control (PWH\n                      <jats:sub>EC<\/jats:sub>\n                      ), 20 HIV progressors (PWH\n                      <jats:sub>PROG<\/jats:sub>\n                      ), and 19 individuals suppressed on ART (PWH\n                      <jats:sub>ART<\/jats:sub>\n                      ). Eighteen individuals without HIV infection (PWOH\n                      <jats:sub>HIV-<\/jats:sub>\n                      ) served as the control group. Monocyte subsets, T cell and monocyte activation and the production of tumour necrosis factor-alpha (TNF-\u03b1), interferon-alpha (IFN-\u03b1), and interleukin-1 beta (IL-1\u03b2) by monocytes, myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells were analyzed using multicolour flow cytometry following stimulation with toll-like receptor (TLR)4 (LPS), TLR7\/8 (CL097), and TLR9 (CpG-ODN2216) ligands. Plasma biomarkers, soluble CD14 (sCD14), and D-dimer were assessed using enzyme-linked immunosorbent assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our findings show a reduced expression of CD86 on monocytes of PWH\n                      <jats:sub>EC<\/jats:sub>\n                      (p=0.04) compared to PWOH\n                      <jats:sub>HIV-<\/jats:sub>\n                      . A reduced frequency of the classical monocyte (CD14+CD16) subset in PWH\n                      <jats:sub>EC<\/jats:sub>\n                      (p=0.02) and PWH\n                      <jats:sub>PROG<\/jats:sub>\n                      (p=0.05) compared to PWOH\n                      <jats:sub>HIV-<\/jats:sub>\n                      . TNF-\u03b1 and IL-1\u03b2 production was lower in monocytes and mDCs of PWH\n                      <jats:sub>EC<\/jats:sub>\n                      compared to PWOH\n                      <jats:sub>HIV-<\/jats:sub>\n                      post-stimulation with TLR4, and TLR7\/8 (all p&amp;lt;0.05). Increased sCD14 levels in PWH\n                      <jats:sub>EC<\/jats:sub>\n                      compared to PWOH\n                      <jats:sub>HIV-<\/jats:sub>\n                      (p=0.01) indicate persistent immune activation, whereas increased D-dimer levels in PWH\n                      <jats:sub>PROG<\/jats:sub>\n                      compared to PWH\n                      <jats:sub>ART<\/jats:sub>\n                      (p=0.01) and PWH\n                      <jats:sub>EC<\/jats:sub>\n                      (p=0.04) suggest higher inflammation in PWH\n                      <jats:sub>PROG<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      PWH\n                      <jats:sub>EC<\/jats:sub>\n                      exhibits similar immune responses as other PWH including PWH\n                      <jats:sub>PROG<\/jats:sub>\n                      , their innate immune profiles are characterized by lower levels of monocyte activation, reduced levels of classical monocytes, reduced capacity to produce pro-inflammatory cytokines, and elevated biomarkers associated with unfavourable disease outcomes. These findings highlight the need for continuous monitoring and potential therapeutic interventions to mitigate chronic inflammation in PWH\n                      <jats:sub>EC<\/jats:sub>\n                      . Furthermore, it expands our understanding of complex innate immune cell responses in PWH\n                      <jats:sub>EC<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1603436","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:14:09Z","timestamp":1756268049000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Innate immune dysfunction and persistent activation in South African HIV elite 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