| First Author | Watson VE | Year | 2000 |
| Journal | J Pathol | Volume | 190 |
| Issue | 2 | Pages | 211-20 |
| PubMed ID | 10657021 | Mgi Jnum | J:60286 |
| Mgi Id | MGI:1353127 | Doi | 10.1002/(SICI)1096-9896(200002)190:2<211::AID-PATH530>3.0.CO;2-3 |
| Citation | Watson VE, et al. (2000) Apoptosis in mycobacterium tuberculosis infection in mice exhibiting varied immunopathology. J Pathol 190(2):211-20 |
| abstractText | This study examined mechanisms contributing to pulmonary immunopathology following acute Mycobacterium tuberculosis (MTB) infection in vivo in a murine model. A/J and C57BL/6 mice were intravenously infected with MTB (Erdman). Pathological differences were found between strains, unrelated to pulmonary load of bacilli. A/J mice developed progressive interstitial pneumonitis, while C57BL/6 mice maintained granuloma formation. The contribution of FAS and FAS ligand-mediated apoptosis was assessed via bioluminescent reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemical staining, and TUNEL assessment of DNA fragmentation. Cytokine messages for pulmonary tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), as well as for the lytic molecules perforin and granzyme B, were quantified. Immunohistochemical staining for CD3 receptor was performed to monitor lymphocytic lung infiltration. Soon after infection, A/J mice exhibited increased pulmonary IFN-gamma message, concurrent with the appearance of CD3+ lymphocytes distributed throughout the lung. C57BL/6 mice exhibited perivascular cuffing, with no accompanying increase in IFN-gamma message. A/J mice also had elevated levels of FAS and FAS ligand message and protein early after infection, while the C57BL/6 mice had no increased expression of these molecules. Both strains exhibited qualitatively similar numbers of TUNEL-positive cells throughout infection, with a marked increase on day 7. Apoptotic cells appeared to co-localize with acid fast bacilli. It is therefore proposed that apoptosis during initial granuloma formation following MTB infection may occur through a FAS/FAS ligand-independent pathway. Moreover, a failure of completion of the FAS/FAS ligand-mediated apoptosis pathway in the A/J mice may contribute to inefficient elimination of lymphocytes, thus further aggravating pulmonary pathology. Copyright 2000 John Wiley & Sons, Ltd. |
