Incomplete recovery of pneumococcal CD4 T cell immunity after initiation of antiretroviral therapy in HIV-infected malawian adults.

Autor: Sepako E; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Respiratory Infection Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom., Glennie SJ; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom., Jambo KC; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Respiratory Infection Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom., Mzinza D; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi., Iwajomo OH; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Division of Clinical Sciences, University of Toronto, Ontario, Canada; Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom., Banda D; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi., van Oosterhout JJ; Dignitas International, Zomba, Malawi., A Williams N; Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom., Gordon SB; Respiratory Infection Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom., Heyderman RS; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2014 Jun 24; Vol. 9 (6), pp. e100640. Date of Electronic Publication: 2014 Jun 24 (Print Publication: 2014).
DOI: 10.1371/journal.pone.0100640
Abstrakt: HIV-infected African adults are at a considerably increased risk of life-threatening invasive pneumococcal disease (IPD) which persists despite antiretroviral therapy (ART). Defects in naturally acquired pneumococcal-specific T-cell immunity have been identified in HIV-infected adults. We have therefore determined the extent and nature of pneumococcal antigen-specific immune recovery following ART. HIV-infected adults were followed up at 3, 6 and 12 months after initiating ART. Nasopharyngeal swabs were cultured to determine carriage rates. Pneumococcal-specific CD4 T-cell immunity was assessed by IFN-γ ELISpot, proliferation assay, CD154 expression and intracellular cytokine assay. S. pneumoniae colonization was detected in 27% (13/48) of HIV-infected patients prior to ART. The rates remained elevated after 12 months ART, 41% (16/39) (p = 0.17) and significantly higher than in HIV-uninfected individuals (HIVneg 14%(4/29); p = 0.0147). CD4+ T-cell proliferative responses to pneumococcal antigens increased significantly to levels comparable with HIV-negative individuals at 12 months ART (p = 0.0799). However, recovery of the pneumococcal-specific CD154 expression was incomplete (p = 0.0015) as were IFN-γ ELISpot responses (p = 0.0040) and polyfunctional CD4+ T-cell responses (TNF-α, IL-2 and IFN-γ expression) (p = 0.0040) to a pneumolysin-deficient mutant strain. Impaired control of pneumococcal colonisation and incomplete restoration of pneumococcal-specific immunity may explain the persistently higher risk of IPD amongst HIV-infected adults on ART. Whether vaccination and prolonged ART can overcome this immunological defect and reduce the high levels of pneumococcal colonisation requires further evaluation.
Databáze: MEDLINE
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