title: 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.affiliation: From the School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban, 4001 South Africa.
authors.forename: Md Aejazur
authors.initials: MA
authors.lastname: Rahman
authors.affiliation: From the School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban, 4001 South Africa.
authors.forename: Parveen
authors.initials: P
authors.lastname: Sobia
authors.affiliation: From the School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban, 4001 South Africa.
authors.forename: Ved Prakash
authors.initials: VP
authors.lastname: Dwivedi
authors.affiliation: the Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Aakansha
authors.initials: A
authors.lastname: Bhawsar
authors.affiliation: the Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Dhiraj Kumar
authors.initials: DK
authors.lastname: Singh
authors.affiliation: the North Eastern Region Biotechnology Programme Management Cell, Defense Colony, New Delhi, India.
authors.forename: Pawan
authors.initials: P
authors.lastname: Sharma
authors.affiliation: From the School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban, 4001 South Africa.
authors.forename: Prashini
authors.initials: P
authors.lastname: Moodley
authors.affiliation: the Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.affiliation: the Center for Tuberculosis Research, Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland 21231-1001, and.
authors.forename: William R
authors.initials: WR
authors.lastname: Bishai
authors.affiliation: From the School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban, 4001 South Africa, the Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India gobardhan.das07@gmail.com.
authors.forename: Gobardhan
authors.initials: G
authors.lastname: Das
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; C112817:TlyA protein, Mycobacterium tuberculosis; D037521:Virulence Factors; D016753:Interleukin-10; D018664:Interleukin-12
keywords: Mycobacterium tuberculosis; T helper cells; cytokine; vaccine; virulence factor
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