title: Tumour necrosis factor receptors and apoptosis of alveolar macrophages during early infection with attenuated and virulent Mycobacterium bovis.
abstract: Apoptosis of macrophages has been reported as an effective host strategy to control the growth of intracellular pathogens, including pathogenic mycobacteria. Tumour necrosis factor-α (TNF-α) plays an important role in the modulation of apoptosis of infected macrophages. It exerts its biological activities via two distinct cell surface receptors, TNFR1 and TNFR2, whose extracellular domain can be released by proteolysis forming soluble TNF receptors (sTNFR1 and sTNFR2). The signalling through TNFR1 initiates the majority of the biological functions of TNF-α, leading to either cell death or survival whereas TNFR2 mediates primarily survival signals. Here, the expression of TNF-α receptors and the apoptosis of alveolar macrophages were investigated during the early phase of infection with attenuated and virulent mycobacteria in mice. A significant increase of apoptosis and high expression of TNFR1 were observed in alveolar macrophages at 3 and 7 days after infection with attenuated Mycobacterium bovis but only on day 7 in infection with the virulent M. bovis. Low surface expression of TNFR1 and increased levels of sTNFR1 on day 3 after infection by the virulent strain were associated with reduced rates of apoptotic macrophages. In addition, a significant reduction in apoptosis of alveolar macrophages was observed in TNFR1(-/-) mice at day 3 after bacillus Calmette-Guérin infection. These results suggest a potential role for TNFR1 in mycobacteria-induced alveolar macrophage apoptosis in vivo. In this scenario, shedding of TNFR1 seems to contribute to the modulation of macrophage apoptosis in a strain-dependent manner.
authors.affiliation: Department of Parasitology, Microbiology and Immunology, Biological Sciences Institute, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: Michele F
authors.initials: MF
authors.lastname: Rodrigues
authors.forename: Caio C S
authors.initials: CC
authors.lastname: Alves
authors.forename: Bárbara B M
authors.initials: BB
authors.lastname: Figueiredo
authors.forename: Alice B
authors.initials: AB
authors.lastname: Rezende
authors.forename: Sabine
authors.initials: S
authors.lastname: Wohlres-Viana
authors.forename: Vânia Lúcia da
authors.initials: VL
authors.lastname: Silva
authors.forename: Marco Antônio
authors.initials: MA
authors.lastname: Machado
authors.forename: Henrique C
authors.initials: HC
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000472:pathogenicity*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014774:Virulence
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha
keywords: Mycobacterium bovis; apoptosis; macrophage; tumour necrosis factor receptor 1; tumour necrosis factor receptor 2