Institute of Tropical Medicine Antwerp
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Adaptation of M. tuberculosis to impaired host immunity in HIV-infected patients

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Show simple item record Walter, N. D. en_US de Jong, B. C. en_US Garcia, B. J. en_US Dolganov, G. M. en_US Worodria, W. en_US Byanyima, P. en_US Musisi, E. en_US Huang, L. en_US Chan, E. D. en_US Van, T. T. en_US Antonio, M. en_US Ayorinde, A. en_US Kato-Maeda, M. en_US Nahid, P. en_US Leung, A. M. en_US Yen, A. en_US Fingerlin, T. E. en_US Kechris, K. en_US Strong, M. en_US Voskuil, M. I. en_US Davis, J. L. en_US Schoolnik, G. K. en_US 2017-12-18T12:56:10Z 2017-12-18T12:56:10Z 2016 en_US
dc.identifier.issn 0022-1899 en_US
dc.identifier.doi en_US
dc.identifier.other en_US
dc.identifier.other ITG-B1A; DBM; U-MYCOB; JIF; DOI; PDF; Abstract; DSPACE64 en_US
dc.description.abstract INTRODUCTION: It is unknown whether immunosuppression influences the physiologic state of Mycobacterium tuberculosis (M.tb) in vivo We evaluated the impact of host immunity by comparing M.tb and human transcription in sputum between HIV-infected and uninfected tuberculosis patients. METHODS: We collected pre-treatment sputum from Gambians and Ugandans with acid-fast bacillus smear-positive pulmonary tuberculosis. We quantified expression of 2,179 M.tb genes and 234 human immune genes via qRT-PCR. We summarized genes significantly increased or decreased in key functional categories. RESULTS: 24 of 65 TB patients were HIV-infected. M.tb DosR regulon genes were less highly expressed among HIV-infected tuberculosis patients than among HIV-uninfected tuberculosis patients (The Gambia: p<0.0001; Uganda: p=0.037). In human profiling of the same sputa, HIV-infected patients had 3.4-fold lower expression of interferon gamma (p=0.005), 4.9-fold higher expression of arginase-1 (p=0.0006) and 3.4-fold higher expression of interleukin-10 (p=0.0002) than HIV-uninfected tuberculosis patients. CONCLUSIONS: M.tb in HIV-infected patients had lower expression of the DosR regulon, a critical metabolic and immunomodulatory switch induced by nitric oxide, carbon monoxide and hypoxia. Our human data suggest that decreased DosR expression may result from alternative pathway activation of macrophages with consequent decreased nitric oxide expression and/or by poor granuloma formation with consequent decreased hypoxic stress. en_US
dc.language English en_US
dc.relation.uri en_US
dc.subject HIV en_US
dc.subject Viral diseases en_US
dc.subject Mycobacterium tuberculosis en_US
dc.subject Bacteriology en_US
dc.subject Immunity en_US
dc.title Adaptation of M. tuberculosis to impaired host immunity in HIV-infected patients en_US
dc.type Article en_US
dc.citation.issue 8 en_US
dc.citation.jtitle Journal of Infectious Diseases en_US
dc.citation.volume 214 en_US
dc.citation.pages 1205-1211 en_US
dc.citation.abbreviation J Infect Dis en_US

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