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

作者:Yokobori Noemi*; Sabio y Garcia Carmen A; Geffner Laura; Schierloh Pablo; Lopez Beatriz; Ritacco Viviana; Barrera Lucia; de la Barrera Silvia; del Carmen Saisiain Maria
来源:FEMS Immunology and Medical Microbiology, 2012, 66(3): 363-371.
DOI:10.1111/j.1574-695X.2012.01024.x

摘要

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 (MF) cell death, and the ability to inhibit of MF apoptosis is considered a virulence mechanism. In this study, the ability these two clinical isolates with divergent epidemiology to induce MF cell death was evaluated using whole inactivated bacteria. We showed that gamma-irradiated (I-) strains induced MF 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 MF 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 MF death.