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

Abstract

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.

• Authors: Md Aejazur Rahman, Parveen Sobia, Ved Prakash Dwivedi, Aakansha Bhawsar, Dhiraj Kumar Singh, Pawan Sharma, Prashini Moodley, Luc Van Kaer, William R Bishai, Gobardhan Das
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 23 Pg. 14407-17 (Jun 05 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 25847237 (Publication Type: Journal Article)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Bacterial Proteins
• TlyA protein, Mycobacterium tuberculosis
• Virulence Factors
• Interleukin-10
• Interleukin-12

Topics

• Animals
• Bacterial Proteins (genetics, immunology, physiology)
• Host-Pathogen Interactions
• Interleukin-10 (immunology)
• Interleukin-12 (immunology)
• Lung (immunology, microbiology, pathology)
• Macrophages (immunology, microbiology, pathology)
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mutation
• Mycobacterium tuberculosis (genetics, immunology)
• Th1 Cells (immunology, microbiology, pathology)
• Th17 Cells (immunology, microbiology, pathology)
• Tuberculosis (immunology, pathology)
• Virulence Factors (genetics, immunology)