Macrophage and T lymphocyte apoptosis during experimental pulmonary tuberculosis: their relationship to mycobacterial virulence.
The kinetics of macrophage and T lymphocyte apoptosis were determined in a well-characterized mouse model of pulmonary tuberculosis, comparing strains of intermediate (H37Rv) and high virulence (Beijing strain, code 9501000). Both strains induced a high percentage of apoptotic activated macrophages at days 1 and 3 post infection, although this was twofold lower in Beijing-infected mice. Progressive pneumonia started at day 14 (Beijing) or 21 (H37Rv) post infection. Pneumonic areas contained numerous macrophages with vacuolated cytoplasm (VM). In H37Rv infection few VM were apoptotic (8.7% at day 60), and the percentage was even lower in Beijing infection (1.4% at day 28). A high percentage of VM expressed the anti-apoptotic molecule Bcl-2 (H37Rv, 83%; Beijing, 95%). Both strains induced a progressive increase of apoptotic Th1 lymphocytes, peaking at day 60 in H37Rv infection, or 28 in Beijing infection. The peak was twofold higher in the latter. VM had strong FasL immunostaining, and confocal microscopy showed numerous apoptotic Th1 cells closely associated with them, suggesting that VM might induce apoptosis of Th1 cells. These results support the hypothesis that apoptosis of macrophages is associated with protection, while apoptosis of Th1 cells favors disease progression, and is related to the virulence of the mycobacterial strain.
Ríos-Barrera
Víctor Adolfo
VA
Experimental Pathology Section, Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Tlalpan, Mexico City CP-14000, Mexico.
Campos-Peña
Victoria
V
Aguilar-León
Diana
D
Lascurain
Ledesma Ricardo
LR
Meraz-Ríos
Marco Antonio
MA
Moreno
José
J
Figueroa-Granados
Víctor
V
Hernández-Pando
Rogelio
R
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D003593:Cytoplasm / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D007150:Immunohistochemistry; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D048069:Tumor Necrosis Factors / Q000276:immunology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D048069:Tumor Necrosis Factors; C052617:Bcl2 protein, mouse