Apoptosis inhibition as a strategy of a prosperous multidrug resistant Mycobacterium tuberculosis strain to evade the immune response

YOKOBORI N; LOPEZ B; GEFFNER L; SCHIERLOH P; BALBOA L; ROMERO M; ALEMáN M; RITACCO V; BARRERA L; DE LA BARRERA S; SASIAIN MC

Plovdiv

Congreso; 29th Annual Congress of the European Society of Mycobacteriology; 2008

Purpose of the stud The multidrug resistant Mycobacterium tuberculosis strain M of the Haarlem 2 sublineage has prevailed over other multidrug resistant M. tuberculosis strains in Argentina since it started clonal expansion in the early ‘90s. We have previously observed that strain M induced less apoptosis than strain H37Rv in human monocyte-derived macrophages. his study was aimed to explore further the influence of strain M on macrophage extrinsic and intrinsic apoptotic pathways and on caspase3 activation, their common final effect. Methods Apoptosis was assessed on macrophages pulsed 5 hours with heat-killed bacilli employing Annexin V/PI assay in presence/absence of exogenously added apoptosis inducers/mediators: i) staurosporin (0.5μM) as intrinsic pathway stimulator, ii) rTNF-α (50ng/ml) as major mediator of mycobacteria-induced apoptosis via the extrinsic pathway and iii) PDTC (50 μM) as inhibitor of nuclear factor κB activation in response to TNF. Caspase3 activation was also measured. Results Upon stimulation with staurosporin, strain M induced less macrophage apoptosis than H37Rv (19.1±4.4% vs. 26.6±4.6%, p