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

Subbian S, Pandey R, Soteropoulos P, Rodriguez GM - J Immunol Res (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Mycobacterial Immunity and Pathogenesis, Rutgers, The State University of New Jersey, 225 Warren Street, Newark, NJ 07103, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Intensity plot of network genes differentially expressed in the vaccinated and Mtb-infected mice lungs. (a) Intensity plot of significantly differentially expressed genes involved in the inflammatory response network. (b) Intensity plot of significantly differentially expressed genes involved in the STAT-1 regulon network. (c) Intensity plot of significantly differentially expressed genes involved in the PC metabolism network. (d) Intensity plot of significantly differentially expressed genes involved in the PPAR-γ regulon network. The values plotted in (a)–(d) are different in fold change in the ΔbfrB vaccinated, compared to BCG vaccinated, Mtb-infected mice lungs. Upregulated genes are in red and downregulated genes are in blue. The color scale bar ranges from +2 (red) to −2 (blue).
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fig4: Intensity plot of network genes differentially expressed in the vaccinated and Mtb-infected mice lungs. (a) Intensity plot of significantly differentially expressed genes involved in the inflammatory response network. (b) Intensity plot of significantly differentially expressed genes involved in the STAT-1 regulon network. (c) Intensity plot of significantly differentially expressed genes involved in the PC metabolism network. (d) Intensity plot of significantly differentially expressed genes involved in the PPAR-γ regulon network. The values plotted in (a)–(d) are different in fold change in the ΔbfrB vaccinated, compared to BCG vaccinated, Mtb-infected mice lungs. Upregulated genes are in red and downregulated genes are in blue. The color scale bar ranges from +2 (red) to −2 (blue).

Mentions: Among various biological functions impacted by the enriched set of SDEG, we selected the most statistically significant and potentially relevant to Tb pathogenesis for more detailed network/pathway analysis. The selected networks are inflammatory response, the STAT-1 regulon, phosphatidylcholine (PC) metabolism, and PPAR-γ regulon (Figure 4).


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

Subbian S, Pandey R, Soteropoulos P, Rodriguez GM - J Immunol Res (2015)

Intensity plot of network genes differentially expressed in the vaccinated and Mtb-infected mice lungs. (a) Intensity plot of significantly differentially expressed genes involved in the inflammatory response network. (b) Intensity plot of significantly differentially expressed genes involved in the STAT-1 regulon network. (c) Intensity plot of significantly differentially expressed genes involved in the PC metabolism network. (d) Intensity plot of significantly differentially expressed genes involved in the PPAR-γ regulon network. The values plotted in (a)–(d) are different in fold change in the ΔbfrB vaccinated, compared to BCG vaccinated, Mtb-infected mice lungs. Upregulated genes are in red and downregulated genes are in blue. The color scale bar ranges from +2 (red) to −2 (blue).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig4: Intensity plot of network genes differentially expressed in the vaccinated and Mtb-infected mice lungs. (a) Intensity plot of significantly differentially expressed genes involved in the inflammatory response network. (b) Intensity plot of significantly differentially expressed genes involved in the STAT-1 regulon network. (c) Intensity plot of significantly differentially expressed genes involved in the PC metabolism network. (d) Intensity plot of significantly differentially expressed genes involved in the PPAR-γ regulon network. The values plotted in (a)–(d) are different in fold change in the ΔbfrB vaccinated, compared to BCG vaccinated, Mtb-infected mice lungs. Upregulated genes are in red and downregulated genes are in blue. The color scale bar ranges from +2 (red) to −2 (blue).
Mentions: Among various biological functions impacted by the enriched set of SDEG, we selected the most statistically significant and potentially relevant to Tb pathogenesis for more detailed network/pathway analysis. The selected networks are inflammatory response, the STAT-1 regulon, phosphatidylcholine (PC) metabolism, and PPAR-γ regulon (Figure 4).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Mycobacterial Immunity and Pathogenesis, Rutgers, The State University of New Jersey, 225 Warren Street, Newark, NJ 07103, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus