A role for lymphotoxin β receptor in host defense against Mycobacterium bovis BCG infection

Rudolf Lucas, Fabienne Tacchini-Cottier, Reto Guler, Dominique Vesin, Stephane Jemelin, Maria L. Olleros, Gilles Marchal, Jeffrey L. Browning, Pierre Vassalli, Irene Garcia

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

To investigate the role of membrane lymphotoxin (LT)α1/β2 and its LTβ receptor (LTβR) in the protective immune response to Mycobacterium bovis bacillus Calmette-Guerin (BCG) infection, we have used a soluble fusion molecule (LTβR-IgG1). LTβR-Ig treatment interferes with granuloma formation mainly in the spleen by inhibiting macrophage activation and nitric oxide synthase activity. In addition, a large accumulation of eosinophils was observed in the spleen of LTβR-Ig-treated infected mice. Decreased blood levels of IFN-γ and increased IL-4 were also observed, suggesting that the LTβR pathway is important in BCG infection to favor a Th1 type of immune response. The treatment of transgenic mice expressing high blood levels of a soluble TNFR1-IgG3 fusion protein with LTβR-Ig resulted in a still higher sensitivity to BCG infection, and extensive necrosis in the spleen. In conclusion, these results suggest that the LTβR and the TNFR pathways are not redundant in the course of BCG infection and protective granuloma formation: the LTβR pathway appears to be important in spleen granuloma formation, whereas the TNFR pathway has a predominant role in other tissues.

Original languageEnglish (US)
Pages (from-to)4002-4010
Number of pages9
JournalEuropean Journal of Immunology
Volume29
Issue number12
DOIs
Publication statusPublished - Dec 13 1999
Externally publishedYes

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Keywords

  • Bacillus Calmette-Guerin
  • Granuloma
  • Lymphotoxin β receptor
  • Spleen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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