title: Alveolar macrophages from HIV-infected subjects are resistant to Mycobacterium tuberculosis in vitro.
abstract: HIV-infected individuals frequently develop Mycobacterium tuberculosis (MTB) infection. Alveolar macrophages (AM) are the initial host defense against this organism. We measured MTB growth in AM from normal and HIV-infected subjects after in vitro exposure. Intracellular growth of MTB was reduced in AM from HIV-infected subjects compared with normal macrophages. This was confined to subjects with CD4 counts greater than 200/microl. Growth of avirulent mycobacteria in HIV macrophages was significantly less than virulent MTB. Because avirulent MTB is more sensitive to tumor necrosis factor-alpha (TNF-alpha), we examined the relationship between cytokine secretion and mycobacterial growth. Higher AM spontaneous TNF-alpha secretion was associated with reduced MTB growth in normal AM. This relationship was not seen in HIV-infected subjects, suggesting that other factors contributed to mycobacteria resistance. Mycobacteria-induced TNF-alpha secretion was inversely associated with growth in normal AM but not in HIV-infected subjects. Finally, binding and internalization of MTB was augmented in HIV macrophages compared with normal, demonstrating that reduced intracellular MTB growth was not due to impaired phagocytosis. In conclusion, the increased incidence of MTB infection in HIV-infected subjects does not appear to be due to a defect in macrophage innate immunity.
authors.affiliation: Division of Pulmonary/Critical Care, Department of Medicine, Indiana University Medical Center, 1481 West 10th St., 111P-IU, Indianapolis, IN 46202, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Day
authors.forename: Yana
authors.initials: Y
authors.lastname: Wang
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Knox
authors.forename: Rajamouli
authors.initials: R
authors.lastname: Pasula
authors.forename: William J
authors.initials: WJ
authors.lastname: Martin
authors.forename: Homer L
authors.initials: HL
authors.lastname: Twigg
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002448:Cell Adhesion; D015658:HIV Infections / Q000382:microbiology*; D015497:HIV-1; D006801:Humans; D007113:Immunity, Innate; D016676:Macrophages, Alveolar / Q000382:microbiology*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D010587:Phagocytosis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha