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Updated: Jan 8, 2026

Characterization of Inflammatory Responses During Intranasal Colonization with Streptococcus pneumoniae

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Published on: January 17, 2014

Colonización persistente por neumococo en la infección por VIH en tratamiento antirretroviral asociada a inflamación

Joseph Aston Phiri^1,2, Lusako Lucky Sibale^3,4, Gloria Kapira^3,4

¹Malawi-Liverpool-Wellcome Research Programme, Blantyre, Malawi. jphiri@mlw.mw.

Nature communications

|December 15, 2025

Abstract:

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.

Palabras clave:

VIH TAR inmunidad nasal neumococo inflamación disfunción inmunitaria células inmunitarias portador de neumococo dianas terapéuticas

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