Institute of Tropical Medicine Antwerp
Foundation of Public Utility

Adaptation of M. tuberculosis to impaired host immunity in HIV-infected patients

DSpace/Manakin Repository

Show simple item record

dc.contributor.author Walter, N. D. en_US
dc.contributor.author de Jong, B. C. en_US
dc.contributor.author Garcia, B. J. en_US
dc.contributor.author Dolganov, G. M. en_US
dc.contributor.author Worodria, W. en_US
dc.contributor.author Byanyima, P. en_US
dc.contributor.author Musisi, E. en_US
dc.contributor.author Huang, L. en_US
dc.contributor.author Chan, E. D. en_US
dc.contributor.author Van, T. T. en_US
dc.contributor.author Antonio, M. en_US
dc.contributor.author Ayorinde, A. en_US
dc.contributor.author Kato-Maeda, M. en_US
dc.contributor.author Nahid, P. en_US
dc.contributor.author Leung, A. M. en_US
dc.contributor.author Yen, A. en_US
dc.contributor.author Fingerlin, T. E. en_US
dc.contributor.author Kechris, K. en_US
dc.contributor.author Strong, M. en_US
dc.contributor.author Voskuil, M. I. en_US
dc.contributor.author Davis, J. L. en_US
dc.contributor.author Schoolnik, G. K. en_US
dc.date.accessioned 2017-12-18T12:56:10Z
dc.date.available 2017-12-18T12:56:10Z
dc.date.issued 2016 en_US
dc.identifier.issn 0022-1899 en_US
dc.identifier.doi http://dx.doi.org/10.1093/infdis/jiw364 en_US
dc.identifier.other http://lib.itg.be/pdf/itg/2016/2016jidi1205.pdf en_US
dc.identifier.other ITG-B1A; DBM; U-MYCOB; JIF; DOI; PDF; Abstract; DSPACE64 en_US
dc.identifier.uri http://hdl.handle.net/10390/9927
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 http://www.ncbi.nlm.nih.gov/pubmed/27534685 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


Files in this item

This item appears in the following Collection(s)

Show simple item record