RATIONALE: The risk of developing active tuberculosis in persons with latent Mycobacterium tuberculosis infection is substantially increased shortly after HIV-1 seroconversion. Immune responses in the lung are important to restrict the growth of M. tuberculosis to prevent the development of disease. OBJECTIVES: To investigate innate and adaptive immune responses to M. tuberculosis in bronchoalveolar lavage from HIV-1-infected persons without active tuberculosis. METHODS: Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, HIV-1-uninfected (n = 21) and HIV-1-infected (n = 15) adults. Growth of M. tuberculosis was assessed in monocytes and alveolar macrophages. Cytokine expression by mycobacteria-specific CD4 and CD8 T cells was measured by intracellular cytokine staining or IFN-gamma ELISpot. MEASUREMENTS AND MAIN RESULTS: Mycobacterial growth in monocytes or alveolar macrophages from HIV-1-infected and -uninfected persons did not differ. Total CD4 T-cell frequencies in BAL were lower in HIV-1-infected than in HIV-1-uninfected persons (P < 0.001). Mycobacteria (bacillus Calmette-Guérin)-specific CD4 T-cell responses in BAL were severely impaired: Frequencies of cells expressing IFN-gamma or tumor necrosis factor (TNF)-alpha, as well as polyfunctional cells, expressing IFN-gamma, TNF-alpha, and IL-2 together, were lower in HIV-1-infected persons than in uninfected controls (P < 0.01 for all). CONCLUSIONS: In addition to a total CD4 T-cell deficit, the function of mycobacteria-specific CD4 T cells is significantly impaired in the lung of HIV-1-infected persons, which may account for the HIV-1-associated elevated risk for developing tuberculosis.
RATIONALE: The risk of developing active tuberculosis in persons with latent Mycobacterium tuberculosis infection is substantially increased shortly after HIV-1 seroconversion. Immune responses in the lung are important to restrict the growth of M. tuberculosis to prevent the development of disease. OBJECTIVES: To investigate innate and adaptive immune responses to M. tuberculosis in bronchoalveolar lavage from HIV-1-infected persons without active tuberculosis. METHODS: Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, HIV-1-uninfected (n = 21) and HIV-1-infected (n = 15) adults. Growth of M. tuberculosis was assessed in monocytes and alveolar macrophages. Cytokine expression by mycobacteria-specific CD4 and CD8 T cells was measured by intracellular cytokine staining or IFN-gamma ELISpot. MEASUREMENTS AND MAIN RESULTS: Mycobacterial growth in monocytes or alveolar macrophages from HIV-1-infected and -uninfected persons did not differ. Total CD4 T-cell frequencies in BAL were lower in HIV-1-infected than in HIV-1-uninfected persons (P < 0.001). Mycobacteria (bacillus Calmette-Guérin)-specific CD4 T-cell responses in BAL were severely impaired: Frequencies of cells expressing IFN-gamma or tumor necrosis factor (TNF)-alpha, as well as polyfunctional cells, expressing IFN-gamma, TNF-alpha, and IL-2 together, were lower in HIV-1-infected persons than in uninfected controls (P < 0.01 for all). CONCLUSIONS: In addition to a total CD4 T-cell deficit, the function of mycobacteria-specific CD4 T cells is significantly impaired in the lung of HIV-1-infected persons, which may account for the HIV-1-associated elevated risk for developing tuberculosis.
Authors: M Cailleaux-Cezar; D de A Melo; G M Xavier; C L G de Salles; F C Q de Mello; A Ruffino-Netto; J E Golub; A Efron; R E Chaisson; M B Conde Journal: Int J Tuberc Lung Dis Date: 2009-02 Impact factor: 2.373
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Authors: Kenneth S Knox; Carol Vinton; Chadi A Hage; Lisa M Kohli; Homer L Twigg; Nichole R Klatt; Beth Zwickl; Jeffrey Waltz; Mitchell Goldman; Daniel C Douek; Jason M Brenchley Journal: J Virol Date: 2010-07-07 Impact factor: 5.103
Authors: Thomas J Scriba; Michele Tameris; Erica Smit; Linda van der Merwe; E Jane Hughes; Blessing Kadira; Katya Mauff; Sizulu Moyo; Nathaniel Brittain; Alison Lawrie; Humphrey Mulenga; Marwou de Kock; Lebohang Makhethe; Esme Janse van Rensburg; Sebastian Gelderbloem; Ashley Veldsman; Mark Hatherill; Hendrik Geldenhuys; Adrian V S Hill; Anthony Hawkridge; Gregory D Hussey; Willem A Hanekom; Helen McShane; Hassan Mahomed Journal: Am J Respir Crit Care Med Date: 2012-01-26 Impact factor: 21.405
Authors: Haitao Hu; Martin Nau; Phil Ehrenberg; Agnes-Laurence Chenine; Camila Macedo; Yu Zhou; Z John Daye; Zhi Wei; Maryanne Vahey; Nelson L Michael; Jerome H Kim; Mary Marovich; Silvia Ratto-Kim Journal: Blood Date: 2012-12-20 Impact factor: 22.113