Mycobacterium tuberculosis TlyA Protein Negatively Regulates T Helper (Th) 1 and Th17 Differentiation and Promotes Tuberculosis Pathogenesis.

Rahman MA, Sobia P, Dwivedi VP, Bhawsar A, Singh DK, Sharma P, Moodley P, Van Kaer L, Bishai WR, Das G
J Biol Chem. 2015 290 (23): 14407-17

PMID: 25847237 · PMCID: PMC4505508 · DOI:10.1074/jbc.M115.653600

Mycobacterium tuberculosis, the causative agent of tuberculosis, is an ancient pathogen and a major cause of death worldwide. Although various virulence factors of M. tuberculosis 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. tuberculosis pathogenesis has not been elucidated. Here, we report that TlyA significantly contributes to the pathogenesis of M. tuberculosis. We show that a TlyA mutant M. tuberculosis 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. tuberculosis. Furthermore, compared with wild type M. tuberculosis, TlyA-deficient M. tuberculosis bacteria are more susceptible to autophagy in macrophages. Consequently, animals infected with the TlyA mutant M. tuberculosis organisms exhibited increased host-protective immune responses, reduced bacillary load, and increased survival compared with animals infected with wild type M. tuberculosis. Thus, M. tuberculosis employs TlyA as a host evasion factor, thereby contributing to its virulence.

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

MeSH Terms (15)

Animals Bacterial Proteins Host-Pathogen Interactions Interleukin-10 Interleukin-12 Lung Macrophages Mice, Inbred BALB C Mice, Inbred C57BL Mutation Mycobacterium tuberculosis Th1 Cells Th17 Cells Tuberculosis Virulence Factors

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