title: Macrophage apoptosis in mycobacterial infections.
abstract: Mycobacterial diseases are a major public health concern. In the case of tuberculosis, the problem has been acerbated due to the emergence of drug-resistant strains of Mycobacterium tuberculosis, and Mycobacterium avium is the major opportunistic pathogen in HIV-1 infection in the United States. M. tuberculosis and M. avium replicate in human macrophages and induce apoptosis. Incubation of freshly added uninfected autologous macrophages with apoptotic M. avium-infected macrophages results in 90% inhibition of bacterial growth. Apoptosis also prevents the release of intracellular components and the spread of mycobacterial infection by sequestering the pathogens within apoptotic bodies. Consistent with the model that host cell apoptosis is a defense mechanism against mycobacteria is the finding that the virulent M. tuberculosis strain H37Rv induces substantially less macrophage apoptosis than the attenuated strain H37Ra. Evasion of apoptosis by this pathogen is achieved by enhanced release of sTNFR2 by H37Rv-infected macrophages and subsequent formation of inactive TNF-alpha-TNFR2 complexes. These observations contribute to the hypothesis that apoptosis of the host macrophage is an important defense mechanism in mycobacterial infections, which prevents the spread of the infection.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: C
authors.initials: C
authors.lastname: Fratazzi
authors.forename: R D
authors.initials: RD
authors.lastname: Arbeit
authors.forename: C
authors.initials: C
authors.lastname: Carini
authors.forename: M K
authors.initials: MK
authors.lastname: Balcewicz-Sablinska
authors.forename: J
authors.initials: J
authors.lastname: Keane
authors.forename: H
authors.initials: H
authors.lastname: Kornfeld
authors.forename: H G
authors.initials: HG
authors.lastname: Remold
mesh_terms: D017209:Apoptosis; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D009164:Mycobacterium Infections / Q000276:immunology*