Aggravated infection in mice co-administered with Mycobacterium tuberculosis and the 27-kDa lipoprotein

Avi Hai Hovav; Jacob Mullerad; Alexander Maly; Liuba Davidovitch; Yolanta Fishman; Herve Bercovier

doi:10.1016/j.micinf.2006.02.011

Aggravated infection in mice co-administered with Mycobacterium tuberculosis and the 27-kDa lipoprotein

Avi Hai Hovav, Jacob Mullerad, Alexander Maly, Liuba Davidovitch, Yolanta Fishman, Herve Bercovier^*

^*Corresponding author for this work

Institute of Biomedical Research at the Faculty of Dental Medicine

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

We have previously reported that mice immunized with the mycobacterial 27-kDa lipoprotein were more susceptible to Mycobacterium tuberculosis (Mtb) challenge. We also showed that 27-kDa lipoprotein abrogated the protection afforded by the BCG vaccine when administrated together, suggesting that the 27-kDa lipoprotein may modulate the course of experimental mycobacterial infection. In this study, we address the role of the 27-kDa lipoprotein in modulating the immune response to mycobacteria. Our results show that co-administration of BALB/c mice with Mtb and the 27-kDa lipoprotein (Mtb+27kDa), but not its non-acylated form, increases the susceptibility of mice to Mtb infection. Significantly lower DTH reaction and splenocyte proliferation to PPD stimulation were also observed in Mtb+27kDa-infected mice compared to Mtb-infected mice. Furthermore, during infection, splenocytes and purified T cells lost their ability to proliferate in response to concanavalin A stimulation more rapidly in the Mtb+27kDa-infected mice, which was accompanied by high IFN-γ and NO production, but low TNF-α secretion levels. Addition of l-NMMA, anti-IFN-γ and anti-TNF-α antibodies restored in vitro proliferative responses of T cells from Mtb+27kDa-infected mice. Short-term l-NMMA treatment of Mtb+27kDa-infected mice prevented the 27-kDa-mediated immunosuppression and increase in susceptibility to Mtb. Altogether, these data suggest that the 27-kDa lipoprotein plays a role in Mtb infection by inducing increased suppression of the immune response due to elevated NO production.

Original language	American English
Pages (from-to)	1750-1757
Number of pages	8
Journal	Microbes and Infection
Volume	8
Issue number	7
DOIs	https://doi.org/10.1016/j.micinf.2006.02.011
State	Published - Jun 2006

Bibliographical note

Funding Information:
The work was performed in the Peter A. Krueger P3 laboratory with the generous financial support of Nancy and Lawrence E. Glick. This work was supported by a grant from the CSED. We thank Itai R. Eyal for helpful comments. We also thank Dr. Mark Cayabyab for critical review of this manuscript.

Keywords

Immunosuppression
Lipoprotein
Mycobacterium
Tuberculosis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.micinf.2006.02.011

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@article{9682285473464319af77e332f15524e6,

title = "Aggravated infection in mice co-administered with Mycobacterium tuberculosis and the 27-kDa lipoprotein",

abstract = "We have previously reported that mice immunized with the mycobacterial 27-kDa lipoprotein were more susceptible to Mycobacterium tuberculosis (Mtb) challenge. We also showed that 27-kDa lipoprotein abrogated the protection afforded by the BCG vaccine when administrated together, suggesting that the 27-kDa lipoprotein may modulate the course of experimental mycobacterial infection. In this study, we address the role of the 27-kDa lipoprotein in modulating the immune response to mycobacteria. Our results show that co-administration of BALB/c mice with Mtb and the 27-kDa lipoprotein (Mtb+27kDa), but not its non-acylated form, increases the susceptibility of mice to Mtb infection. Significantly lower DTH reaction and splenocyte proliferation to PPD stimulation were also observed in Mtb+27kDa-infected mice compared to Mtb-infected mice. Furthermore, during infection, splenocytes and purified T cells lost their ability to proliferate in response to concanavalin A stimulation more rapidly in the Mtb+27kDa-infected mice, which was accompanied by high IFN-γ and NO production, but low TNF-α secretion levels. Addition of l-NMMA, anti-IFN-γ and anti-TNF-α antibodies restored in vitro proliferative responses of T cells from Mtb+27kDa-infected mice. Short-term l-NMMA treatment of Mtb+27kDa-infected mice prevented the 27-kDa-mediated immunosuppression and increase in susceptibility to Mtb. Altogether, these data suggest that the 27-kDa lipoprotein plays a role in Mtb infection by inducing increased suppression of the immune response due to elevated NO production.",

keywords = "Immunosuppression, Lipoprotein, Mycobacterium, Tuberculosis",

author = "Hovav, {Avi Hai} and Jacob Mullerad and Alexander Maly and Liuba Davidovitch and Yolanta Fishman and Herve Bercovier",

note = "Funding Information: The work was performed in the Peter A. Krueger P3 laboratory with the generous financial support of Nancy and Lawrence E. Glick. This work was supported by a grant from the CSED. We thank Itai R. Eyal for helpful comments. We also thank Dr. Mark Cayabyab for critical review of this manuscript.",

year = "2006",

month = jun,

doi = "10.1016/j.micinf.2006.02.011",

language = "American English",

volume = "8",

pages = "1750--1757",

journal = "Microbes and Infection",

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T1 - Aggravated infection in mice co-administered with Mycobacterium tuberculosis and the 27-kDa lipoprotein

AU - Hovav, Avi Hai

AU - Mullerad, Jacob

AU - Maly, Alexander

AU - Davidovitch, Liuba

AU - Fishman, Yolanta

AU - Bercovier, Herve

N1 - Funding Information: The work was performed in the Peter A. Krueger P3 laboratory with the generous financial support of Nancy and Lawrence E. Glick. This work was supported by a grant from the CSED. We thank Itai R. Eyal for helpful comments. We also thank Dr. Mark Cayabyab for critical review of this manuscript.

PY - 2006/6

Y1 - 2006/6

N2 - We have previously reported that mice immunized with the mycobacterial 27-kDa lipoprotein were more susceptible to Mycobacterium tuberculosis (Mtb) challenge. We also showed that 27-kDa lipoprotein abrogated the protection afforded by the BCG vaccine when administrated together, suggesting that the 27-kDa lipoprotein may modulate the course of experimental mycobacterial infection. In this study, we address the role of the 27-kDa lipoprotein in modulating the immune response to mycobacteria. Our results show that co-administration of BALB/c mice with Mtb and the 27-kDa lipoprotein (Mtb+27kDa), but not its non-acylated form, increases the susceptibility of mice to Mtb infection. Significantly lower DTH reaction and splenocyte proliferation to PPD stimulation were also observed in Mtb+27kDa-infected mice compared to Mtb-infected mice. Furthermore, during infection, splenocytes and purified T cells lost their ability to proliferate in response to concanavalin A stimulation more rapidly in the Mtb+27kDa-infected mice, which was accompanied by high IFN-γ and NO production, but low TNF-α secretion levels. Addition of l-NMMA, anti-IFN-γ and anti-TNF-α antibodies restored in vitro proliferative responses of T cells from Mtb+27kDa-infected mice. Short-term l-NMMA treatment of Mtb+27kDa-infected mice prevented the 27-kDa-mediated immunosuppression and increase in susceptibility to Mtb. Altogether, these data suggest that the 27-kDa lipoprotein plays a role in Mtb infection by inducing increased suppression of the immune response due to elevated NO production.

AB - We have previously reported that mice immunized with the mycobacterial 27-kDa lipoprotein were more susceptible to Mycobacterium tuberculosis (Mtb) challenge. We also showed that 27-kDa lipoprotein abrogated the protection afforded by the BCG vaccine when administrated together, suggesting that the 27-kDa lipoprotein may modulate the course of experimental mycobacterial infection. In this study, we address the role of the 27-kDa lipoprotein in modulating the immune response to mycobacteria. Our results show that co-administration of BALB/c mice with Mtb and the 27-kDa lipoprotein (Mtb+27kDa), but not its non-acylated form, increases the susceptibility of mice to Mtb infection. Significantly lower DTH reaction and splenocyte proliferation to PPD stimulation were also observed in Mtb+27kDa-infected mice compared to Mtb-infected mice. Furthermore, during infection, splenocytes and purified T cells lost their ability to proliferate in response to concanavalin A stimulation more rapidly in the Mtb+27kDa-infected mice, which was accompanied by high IFN-γ and NO production, but low TNF-α secretion levels. Addition of l-NMMA, anti-IFN-γ and anti-TNF-α antibodies restored in vitro proliferative responses of T cells from Mtb+27kDa-infected mice. Short-term l-NMMA treatment of Mtb+27kDa-infected mice prevented the 27-kDa-mediated immunosuppression and increase in susceptibility to Mtb. Altogether, these data suggest that the 27-kDa lipoprotein plays a role in Mtb infection by inducing increased suppression of the immune response due to elevated NO production.

KW - Immunosuppression

KW - Lipoprotein

KW - Mycobacterium

KW - Tuberculosis

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DO - 10.1016/j.micinf.2006.02.011

M3 - Article

C2 - 16815070

AN - SCOPUS:33746436594

SN - 1286-4579

VL - 8

SP - 1750

EP - 1757

JO - Microbes and Infection

JF - Microbes and Infection

IS - 7

ER -

Aggravated infection in mice co-administered with Mycobacterium tuberculosis and the 27-kDa lipoprotein

Abstract

Bibliographical note

Keywords

UN SDGs

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