TY - JOUR
T1 - A role for lymphotoxin β receptor in host defense against Mycobacterium bovis BCG infection
AU - Lucas, Rudolf
AU - Tacchini-Cottier, Fabienne
AU - Guler, Reto
AU - Vesin, Dominique
AU - Jemelin, Stephane
AU - Olleros, Maria L.
AU - Marchal, Gilles
AU - Browning, Jeffrey L.
AU - Vassalli, Pierre
AU - Garcia, Irene
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Bacillus Calmette-Guerin
KW - Granuloma
KW - Lymphotoxin β receptor
KW - Spleen
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U2 - 10.1002/(SICI)1521-4141(199912)29:12<4002::AID-IMMU4002>3.0.CO;2-S
DO - 10.1002/(SICI)1521-4141(199912)29:12<4002::AID-IMMU4002>3.0.CO;2-S
M3 - Article
C2 - 10602010
AN - SCOPUS:0032709799
SN - 0014-2980
VL - 29
SP - 4002
EP - 4010
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 12
ER -