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Ann Am Thorac Soc. 2015 Nov;12(11):1627-37. doi: 10.1513/AnnalsATS.201507-463OC.

Effect of Antiretroviral Therapy on HIV-mediated Impairment of the Neutrophil Antimycobacterial Response.

Author information

1
1 Clinical Infectious Diseases Research Initiative, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
2
2 Department of Medicine, Imperial College London, London, United Kingdom.
3
3 Institute of Immunity and Transplantation, University College London, Royal Free Hospital Campus, London, United Kingdom.
4
4 Vaccines and Immunity Theme, Medical Research Council Unit, The Gambia, West Africa.
5
5 Francis Crick Institute Mill Hill Laboratory, London, United Kingdom; and.
6
6 Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.

Abstract

RATIONALE:

Experimental and epidemiological evidence suggests that neutrophils are important in the host response to tuberculosis. HIV infection, which increases the risk of tuberculosis, adversely affects neutrophil function.

OBJECTIVES:

To determine the impact of HIV and antiretroviral therapy on neutrophil antimycobacterial activity.

METHODS:

We performed a cross-sectional comparison of neutrophil functions in 20 antiretroviral-naive HIV-infected and 20 HIV-uninfected individuals using luminescence-, flow cytometry-, and ELISA-based assays. We then conducted a prospective study in the HIV-infected individuals investigating these parameters during the first 6 months of antiretroviral therapy. Surface markers of neutrophil activation were investigated in a separate cohort using flow cytometry.

MEASUREMENTS AND MAIN RESULTS:

HIV infection impaired control of Mycobacterium tuberculosis by neutrophils (mean ratio of mycobacterial luminescence in neutrophil samples vs. serum controls at 1 hour in HIV-infected participants, 0.88 ± 0.13 vs. HIV-uninfected participants, 0.76 ± 0.14; P = 0.01; at 24 hours, 0.82 ± 0.13 vs. 0.71 ± 0.13; P = 0.01). The extent of impairment correlated with log[HIV viral load]. Neutrophil cell death after 24 hours' incubation with M. tuberculosis was higher in the HIV-infected cohort (85.3 ± 11.8% vs. 57.9 ± 22.4% necrotic cells; P < 0.0001). Neutrophils from HIV-infected participants demonstrated significantly more CD62L-negative cells (median, 23.0 vs. 8.5%; P = 0.008) and CD16-negative cells (3.2 vs. 1.3%, P = 0.03). Antiretroviral therapy restored mycobacterial restriction and pattern of neutrophil death toward levels seen in HIV-uninfected persons.

CONCLUSIONS:

Neutrophils in antiretroviral-naive HIV-infected persons are hyperactivated, eliminate M. tuberculosis less effectively than in HIV-uninfected individuals, and progress rapidly to necrotic cell death. These factors are ameliorated by antiretroviral therapy.

KEYWORDS:

granulocyte; necrosis; tuberculosis

PMID:
26368270
PMCID:
PMC4724897
DOI:
10.1513/AnnalsATS.201507-463OC
[Indexed for MEDLINE]
Free PMC Article

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