Mycobacterium tuberculosis TlyA Protein Negatively Regulates T Helper (Th) 1 and Th17 Differentiation and Promotes Tuberculosis Pathogenesis
Authors: Parveen Sobia
Luc Van Kaer
William R Bishai
Prashini Moodley
Aakansha Bhawsar
Pawan Sharma
Gobardhan Das
Dhiraj Kumar Singh
Ved Prakash Dwivedi
Md Aejazur Rahman
Journal: Journal of Biological Chemistry (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Mycobacterium tuberculosis; T helper cells; cytokine; vaccine; virulence factor.
Affiliations: 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., the North Eastern Region Biotechnology Programme Management Cell, Defense Colony, New Delhi, India., the Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232., the Center for Tuberculosis Research, Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland 21231-1001, and., 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 .

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. 

Retracted: No

PubPeer comments:
 Fig 2D: UI plots are duplicates ![file] Also, has the quality of the JBC images decreased significantly now that they are hosted by Elsevier? , 
 ![file] I do not agree that both of the figures are same. Some of the differences are highlighted although there are many. At a glance they may look similar, may be because the sample type is same or x axis has same stain or samples were run simultaneously or it is just a single multiparametric reaction (generally it happens). Even in a single reaction, we can get two values for x-axis (IFN-gamma in this case) because it also depends on the color at y axis (compensation is never 100% perfect). Therefore, the negative cells may look like same. However, cells that are positive for IL-4 or IL-17 are different. , 
 I agree with Cregya Oculata s comment in #1. These two panels look unexpectedly similar. Yet, the gated percentages are different. The authors can take away any concern by posting high resolution, original files here. , 
 #2 Possibly helpful: an animated comparison of the two panels (click to animate). The panels share most of their points and the few differences may be attributable to compression artifacts. I second #3: high resolution originals would be helpful. ![file] ,