Shift in the phenotype of infiltrating macrophages towards M2 subset is related to Bcl-2 expression in the myocardium during Trypanosoma cruzi experimental infection

PONCE N.E.; CANO R.C.; GEA S.; AOKI M.P.

Londres

Congreso; Annual Congress of the British Society for Immunology; 2011

British Society for Immunology

Infection with the cardiotropic parasite Trypanosoma cruzi causes Chagas? disease, the leading infectious cardiomyopathy in the world. Macrophage (Ma) influx to the infected myocardium could participate either in defense/pathogenesis or repair mechanisms. The M1 pro-inflammatory phenotype (F4/80+ CD68+) participates in the elimination of the parasite whereas the M2 anti-inflammatory phenotype (F4/80+ CD206+) attenuates the inflammatory response and promotes tissue repair. We studied the kinetic of both infiltrating Ma subsets by flow cytometry and the expression of the anti-apoptotic molecule Bcl-2 by western blot and inmunofluorescence in the myocardium of BALB/c mice infected with T. cruzi Tulahuen strain. We found a clear predominance of Ma with M1 profile at 4 days post-infection (dpi) (84±16% vs M2 16±15%, p< 0.005). In contrast, at 7, 14, 21 and 23 dpi the M1 population diminished significantly (15±7%, 6±3%, 3±3% and 0.8±0.4% respectively) being strongly increased the M2 phenotype (85±7%, 94±3%, 97±3% and 99.2±0.4%, p< 0.001 vs M1 for each time). Moreover, an important F4/80+ CD68+ and CD206+ population was observed (77±5%, 71±6%, 71.3±0.8%, 66±10% and 69±3% respectively). In addition, Bcl-2 exhibited a basal expression in control non-infected myocardial tissue, whereas it significantly increased at 21 and 24 dpi (3.7±0.7 and 3.8±1.3 folds; p< 0.05 vs control). This protein was mainly restricted to cardiomyocytes and, to a lesser extent, inflammatory cells. Conclusion: A shift in the phenotype of infiltrating Ma from a predominant M1 towards a M2 subset occurs during T. cruzi acute infection. In parallel with M2 appearance, Bcl-2 increased its expression in cardiomyocytes.