Vaccination with an Attenuated Ferritin Mutant Protects Mice against Virulent Mycobacterium tuberculosis

Mycobacterium tuberculosis the causative agent of tuberculosis affects millions of people worldwide. New tools for treatment and prevention of tuberculosis are urgently needed. We previously showed that a ferritin (bfrB) mutant of M. tuberculosis has altered iron homeostasis and increased sensitivit...

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Main Authors: Selvakumar Subbian, Ruchi Pandey, Patricia Soteropoulos, G. Marcela Rodriguez
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2015/385402
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author Selvakumar Subbian
Ruchi Pandey
Patricia Soteropoulos
G. Marcela Rodriguez
author_facet Selvakumar Subbian
Ruchi Pandey
Patricia Soteropoulos
G. Marcela Rodriguez
author_sort Selvakumar Subbian
collection DOAJ
description Mycobacterium tuberculosis the causative agent of tuberculosis affects millions of people worldwide. New tools for treatment and prevention of tuberculosis are urgently needed. We previously showed that a ferritin (bfrB) mutant of M. tuberculosis has altered iron homeostasis and increased sensitivity to antibiotics and to microbicidal effectors produced by activated macrophages. Most importantly, M. tuberculosis lacking BfrB is strongly attenuated in mice, especially, during the chronic phase of infection. In this study, we examined whether immunization with a bfrB mutant could confer protection against subsequent infection with virulent M. tuberculosis in a mouse model. The results show that the protection elicited by immunization with the bfrB mutant is comparable to BCG vaccination with respect to reduction of bacterial burden. However, significant distinctions in the disease pathology and host genome-wide lung transcriptome suggest improved containment of Mtb infection in animals vaccinated with the bfrB mutant, compared to BCG. We found that downmodulation of inflammatory response and enhanced fibrosis, compared to BCG vaccination, is associated with the protective response elicited by the bfrB mutant.
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spelling doaj-art-ef1e0e68ce9642019180c8d1445a3c2d2025-02-03T06:07:32ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/385402385402Vaccination with an Attenuated Ferritin Mutant Protects Mice against Virulent Mycobacterium tuberculosisSelvakumar Subbian0Ruchi Pandey1Patricia Soteropoulos2G. Marcela Rodriguez3Laboratory of Mycobacterial Immunity and Pathogenesis, Rutgers, The State University of New Jersey, 225 Warren Street, Newark, NJ 07103, USAPublic Health Research Institute at Rutgers Biomedical and Health Sciences, Rutgers, The State University of New Jersey, 225 Warren Street, Newark, NJ 07103, USAPublic Health Research Institute at Rutgers Biomedical and Health Sciences, Rutgers, The State University of New Jersey, 225 Warren Street, Newark, NJ 07103, USAPublic Health Research Institute at Rutgers Biomedical and Health Sciences, Rutgers, The State University of New Jersey, 225 Warren Street, Newark, NJ 07103, USAMycobacterium tuberculosis the causative agent of tuberculosis affects millions of people worldwide. New tools for treatment and prevention of tuberculosis are urgently needed. We previously showed that a ferritin (bfrB) mutant of M. tuberculosis has altered iron homeostasis and increased sensitivity to antibiotics and to microbicidal effectors produced by activated macrophages. Most importantly, M. tuberculosis lacking BfrB is strongly attenuated in mice, especially, during the chronic phase of infection. In this study, we examined whether immunization with a bfrB mutant could confer protection against subsequent infection with virulent M. tuberculosis in a mouse model. The results show that the protection elicited by immunization with the bfrB mutant is comparable to BCG vaccination with respect to reduction of bacterial burden. However, significant distinctions in the disease pathology and host genome-wide lung transcriptome suggest improved containment of Mtb infection in animals vaccinated with the bfrB mutant, compared to BCG. We found that downmodulation of inflammatory response and enhanced fibrosis, compared to BCG vaccination, is associated with the protective response elicited by the bfrB mutant.http://dx.doi.org/10.1155/2015/385402
spellingShingle Selvakumar Subbian
Ruchi Pandey
Patricia Soteropoulos
G. Marcela Rodriguez
Vaccination with an Attenuated Ferritin Mutant Protects Mice against Virulent Mycobacterium tuberculosis
Journal of Immunology Research
title Vaccination with an Attenuated Ferritin Mutant Protects Mice against Virulent Mycobacterium tuberculosis
title_full Vaccination with an Attenuated Ferritin Mutant Protects Mice against Virulent Mycobacterium tuberculosis
title_fullStr Vaccination with an Attenuated Ferritin Mutant Protects Mice against Virulent Mycobacterium tuberculosis
title_full_unstemmed Vaccination with an Attenuated Ferritin Mutant Protects Mice against Virulent Mycobacterium tuberculosis
title_short Vaccination with an Attenuated Ferritin Mutant Protects Mice against Virulent Mycobacterium tuberculosis
title_sort vaccination with an attenuated ferritin mutant protects mice against virulent mycobacterium tuberculosis
url http://dx.doi.org/10.1155/2015/385402
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