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

Research output: Contribution to journalArticlepeer-review

14 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 languageAmerican English
Pages (from-to)1750-1757
Number of pages8
JournalMicrobes and Infection
Volume8
Issue number7
DOIs
StatePublished - 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

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