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<p>Despite systemic viral suppression, people living with HIV (PLHIV) on antiretroviral therapy (ART) remain highly susceptible to pneumococcal colonisation and disease. Here, we show that long-term ART does not restore nasal mucosal immunity. Using flow cytometry, single-cell transcriptomics, and neutrophil functional assays, we identify a persistent mucosal immune signature in PLHIV-ART &gt; 1 yr marked by epithelial-driven neutrophilic inflammation, T cell exhaustion, and cellular senescence. Neutrophils exhibit mitochondrial stress, senescence-associated secretory phenotype (SASP) gene expression, and impaired oxidative burst, particularly in individuals with pneumococcal carriage. Epithelial cells express elevated neutrophil-recruiting ligand genes, while nasal T cells display pro-apoptotic and exhaustion gene profiles. Neutrophilic inflammation is strongly associated with pneumococcal carriage density, implicating a feedforward loop between inflammation and microbial persistence. Our findings reveal tissue-specific immune dysregulation despite ART and suggest that targeting epithelial-immune signalling or neutrophil senescence may offer novel therapeutic avenues to reduce respiratory pathogen burden in PLHIV.</p>

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Persistent pneumococcal colonisation in antiretroviral-treated HIV infection is associated with nasal inflammation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月15日

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  • Joseph Aston Phiri,
  • Lusako Lucky Sibale,
  • Gloria Kapira,
  • Lukerensia Mlogoti,
  • James Tchado Nyirenda,
  • Ndaona Mitole,
  • Alice Kusakala,
  • Charles Ndovi,
  • Precious Chigamba,
  • Aaron Pearson Chirambo,
  • Klara Doherty,
  • Robert K. Nyirenda,
  • Thokozani Kayembe,
  • Janet Zambezi,
  • Edwin Lisimba,
  • Memory Nekati Mvula,
  • David Viyezgo Mhango,
  • Leonard Mvaya,
  • Stephen B. Gordon,
  • Benjamin Kumwenda,
  • Christopher Moxon,
  • Daniela M. Ferreira,
  • Henry C. Mwandumba,
  • Kondwani C. Jambo

摘要

Despite systemic viral suppression, people living with HIV (PLHIV) on antiretroviral therapy (ART) remain highly susceptible to pneumococcal colonisation and disease. Here, we show that long-term ART does not restore nasal mucosal immunity. Using flow cytometry, single-cell transcriptomics, and neutrophil functional assays, we identify a persistent mucosal immune signature in PLHIV-ART > 1 yr marked by epithelial-driven neutrophilic inflammation, T cell exhaustion, and cellular senescence. Neutrophils exhibit mitochondrial stress, senescence-associated secretory phenotype (SASP) gene expression, and impaired oxidative burst, particularly in individuals with pneumococcal carriage. Epithelial cells express elevated neutrophil-recruiting ligand genes, while nasal T cells display pro-apoptotic and exhaustion gene profiles. Neutrophilic inflammation is strongly associated with pneumococcal carriage density, implicating a feedforward loop between inflammation and microbial persistence. Our findings reveal tissue-specific immune dysregulation despite ART and suggest that targeting epithelial-immune signalling or neutrophil senescence may offer novel therapeutic avenues to reduce respiratory pathogen burden in PLHIV.