Increased Bcl-2 and reduced Bax expression in infected macrophages in slowly progressive primary murine Mycobacterium tuberculosis infection.
Mycobacterium tuberculosis (MTB) persists in host macrophages (Mphis) because it has developed mechanisms to escape Mphi killing. In vitro studies have shown that MTB can induce and inhibit apoptosis by causing the expression of Bax and Bcl-2, respectively, suggesting that the infected cells' fate depends on pro- and antiapoptotic signals. In the present study, we investigated the role of Bcl-2 in MTB infection in situ. The aim was to study the pattern and distribution of Bcl-2 and Bax in cellular infiltrates of MTB-infected B6D2F1 hybrid mice and correlate the expression with the presence of MTB antigens (MAgs). Using formalin-fixed lung tissues (n = 45), our results showed a significant difference in the percentage of Mphis stained for Bcl-2 or MAgs and Bax (P < 0.0001). Bcl-2 expression was increased in a population of Mphis and corresponded in intensity, colocalization and percentage with that of MAgs on the same cells, while Bax expression was reduced. In lymphocyte aggregates, Bcl-2 and Bax did not show any differences. We conclude that overexpression of Bcl-2 in Mphis containing MTB may be associated with intracellular survival of the bacilli, thus demonstrating one way by which MTB can escape the host's cellular response and killing.
Mogga
S J
SJ
Centre for International Health, Broegelmann Research Laboratory and Institute of Dentistry, University of Bergen, Norway. mogga.josephson@cih.uib.no
Mustafa
T
T
Sviland
L
L
Nilsen
R
R
D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis; D017209:Apoptosis / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D019254:Genes, bcl-2; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D014395:Peritonitis, Tuberculous / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein
D000942:Antigens, Bacterial; C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein