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Adaptation of Mycobacterium tuberculosis to Impaired Host Immunity in HIV-Infected Patients.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2016 Oct 15; Vol. 214 (8), pp. 1205-11. Date of Electronic Publication: 2016 Aug 17. - Publication Year :
- 2016
-
Abstract
- Background: It is unknown whether immunosuppression influences the physiologic state of Mycobacterium tuberculosis in vivo. We evaluated the impact of host immunity by comparing M. tuberculosis and human gene transcription in sputum between human immunodeficiency virus (HIV)-infected and uninfected patients with tuberculosis.<br />Methods: We collected sputum specimens before treatment from Gambians and Ugandans with pulmonary tuberculosis, revealed by positive results of acid-fast bacillus smears. We quantified expression of 2179 M. tuberculosis genes and 234 human immune genes via quantitative reverse transcription-polymerase chain reaction. We summarized genes from key functional categories with significantly increased or decreased expression.<br />Results: A total of 24 of 65 patients with tuberculosis were HIV infected. M. tuberculosis DosR regulon genes were less highly expressed among HIV-infected patients with tuberculosis than among HIV-uninfected patients with tuberculosis (Gambia, P < .0001; Uganda, P = .037). In profiling of human genes from the same sputa, HIV-infected patients had 3.4-fold lower expression of IFNG (P = .005), 4.9-fold higher expression of ARG1 (P = .0006), and 3.4-fold higher expression of IL10 (P = .0002) than in HIV-uninfected patients with tuberculosis.<br />Conclusions: M. tuberculosis in HIV-infected patients had lower expression of the DosR regulon, a critical metabolic and immunomodulatory switch induced by NO, carbon monoxide, and hypoxia. Our human data suggest that decreased DosR expression may result from alternative pathway activation of macrophages, with consequent decreased NO expression and/or by poor granuloma formation with consequent decreased hypoxic stress.<br /> (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)
- Subjects :
- Adult
Bacterial Proteins genetics
DNA-Binding Proteins
Gambia
Granuloma genetics
Granuloma immunology
Granuloma microbiology
HIV Infections genetics
Humans
Hypoxia immunology
Hypoxia microbiology
Macrophages immunology
Macrophages microbiology
Mycobacterium tuberculosis genetics
Nitrogen Oxides immunology
Protein Kinases genetics
Regulon genetics
Regulon immunology
Sputum microbiology
Transcription, Genetic genetics
Transcription, Genetic immunology
Tuberculosis, Pulmonary genetics
Tuberculosis, Pulmonary microbiology
Uganda
Adaptation, Physiological immunology
HIV Infections immunology
HIV Infections microbiology
Mycobacterium tuberculosis immunology
Tuberculosis, Pulmonary immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 214
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 27534685
- Full Text :
- https://doi.org/10.1093/infdis/jiw364