Differential induction of macrophage cell death by antigens of a clustered and a non-clustered multidrug-resistant Mycobacterium tuberculosis strain from Haarlem family.
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 (MΦ) cell death, and the ability to inhibit of MΦ apoptosis is considered a virulence mechanism. In this study, the ability these two clinical isolates with divergent epidemiology to induce MΦ cell death was evaluated using whole inactivated bacteria. We showed that gamma-irradiated (I-) strains induced MΦ 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 MΦ 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 MΦ death.
Instituto de Medicina Experimental-CONICET, Buenos Aires, Argentina. kaoru.noemi@gmail.com
Noemí
N
Yokobori
Carmen A
CA
Sabio y García
Laura
L
Geffner
Pablo
P
Schierloh
Beatriz
B
López
Viviana
V
Ritacco
Lucía
L
Barrera
Silvia
S
de la Barrera
María
M
del Carmen Saisiain
D000942:Antigens, Bacterial / Q000276:immunology*; D001118:Argentina; D016923:Cell Death; D002478:Cells, Cultured; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000276:immunology* / Q000472:pathogenicity; D014376:Tuberculosis / Q000382:microbiology
D000942:Antigens, Bacterial