Differential induction of macrophage cell death by antigens of a clustered and a non-clustered multidrug-resistant Mycobacterium tuberculosis strain from Haarlem family

YOKOBORI N; SABIO Y GARCÍA C; GEFFNER L; SCHIERLOH P; LÓPEZ B; RITACCO V; BARRERA L; DE LA BARRERA S; SASIAIN M

FEMS Immunology & Medical Microbiology

Wiley-Blackwell

Año: 2012 vol. 66 p. 363 - 371

1574-695X

Some multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) genotypes are the cause of large outbreaks, including strain M identified in Argentina. In contrast, its kin strain 410 has only caused a single case to date. Cell wall antigens from Mtb were associated with the modulation of macrophage cell death, and the ability to inhibit of macrophage apoptosis is considered a virulence mechanism. In this study, the ability these two clinical isolates with divergent epidemiology to induce macrophage cell death was evaluated using whole inactivated bacteria. We showed that gamma-irradiated (I-) strains induced macrophage necrosis, the strongest inducer being I-410. Cell death biased towards apoptosis with the heat-killed (hk) strains, both hk-MDR strains being poorer inducers of Macrophages apoptosis than was H37Rv. These effects were partly due to their ability to induce anti-apoptotic mechanisms which were not related to the lack of tumor necrosis factor alpha induction or a compensatory effect of interleukin-10. The most noticeable difference between strain M and strain 410 was the ability shown by hk-M to interfere with apoptosis induced by hk-H37Rv. Thus, heat-stable and heat-labile antigens from these epidemiologically divergent Mtb strains differ in their ability to manipulate macrophage death.