Mycobacterium tuberculosis TlyA negatively regulates Th1 and Th17 differentiation and promotes tuberculosis pathogenesis [Cell Biology]
April 6th, 2015 by Rahman, M. A., Sobia, P., Dwivedi, V. P., Bhawsar, A., Singh, D. K., Sharma, P., Moodley, P., Kaer, L. V., Bishai, W. R., Das, G.
Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, is an ancient pathogen and a major cause of death worldwide. Although various virulence factors of M.tb have been identified, its pathogenesis remains incompletely understood. TlyA is a virulence factor in several bacterial infections and is evolutionarily conserved in many gram-positive bacteria, but its function in M.tb pathogenesis has not been elucidated. Here, we report that TlyA significantly contributes to the pathogenesis of M.tb. We show that a TlyA mutant M.tb strain induces increased IL-12 and reduced IL-1β and IL-10 cytokine responses, which sharply contrasts with the immune responses induced by wild type M.tb. Furthermore, compared with wild type M.tb, TlyA-deficient M.tb bacteria are more susceptible to autophagy in macrophages. Consequently, animals infected with TlyA mutant M.tb organisms exhibited increased host protective immune responses, reduced bacillary load, and increased survival compared with animals infected with wild type M.tb. Thus, M.tb employs TlyA as a host evasion factor, thereby contributing to its virulence.