The virulence of multidrug-resistant Mycobacterium tuberculosis strain M is related to its low replication rate and delayed cytokine production

NOEMI YOKOBORI; BEATRIZ LOPEZ; CARMEN SABIO Y GARCIA; PABLO SCHIERLOH; VIVIANA RITACCO; LUCIA BARRERA; MARIA DEL CARMEN SASIAIN

Congreso; 14th International Congress of Immunology; 2010

Multidrug-resistant tuberculosis (MDR-TB) is a mayor threat to public health. Argentina was declared as a “hot spot” for MDR-TB due to extensive outbreaks that emerged in the 90’s, mainly due to the aggressive spread of strain M, a highly successful genotype that persists even in our days. In order to explain its high virulence, the intracellular growth of strain M was compared to that of strain 410, another Haarlem strain closely related to M according to the RFLP pattern, but isolated just once. Human monocyte derived macrophages were infected with strain M, 410 and the reference strain H37Rv for four hours at a multiplicity of infection of 10, and cell-associated colony forming units (CFU) were assessed at 0, 2 and 5 days of infection in 7H9/OADC medium. At the same time points, intracellular bacillary load was revealed with Ziehl-Neelsen stain and supernatants were collected to determine the secretion of TNF-á and IL-10 by ELISA. The initial percentage of infected cells was similar with both MDR strains (M: 52±4%; 410: 51±3) and lower than H37Rv (60±4; p<0.05). However, strain 410 grew faster than M (Day 5, M: 1470±160 CFU/ml; 410: 2490±210; H37Rv: 1740±300, Mean±SEM. M vs. 410: p<0.05). Moreover, strain 410 induced an early production of TNF-á and IL-10. Our results demonstrate that the intracellular growth of strain M was slower than 410, which is in contrast to the Beijing family isolates. Besides, TNF-á and IL-10 production by M was delayed. The epidemiological success of M may relay on these characteristics.