The resistance against Listeria monocytogenes and the formation of germinal centers depend on a functional death domain of the 55 kDa tumor necrosis factor receptor

Abstract

The biological functions mediated by the death domain of the 55-kDa tumor necrosis factor receptor (TNFRp55) in vivo are still elusive. TNFRp55 mutants lacking a functional death domain were expressed in TNFRp55(-/-) and in TNFRp55(+/-) mice as transgenes under control of the H-2Kb promoter. Analysis of these animals revealed that signals originating from the TNFRp55 death domain are indispensable for the protection against Listeria monocytogenes, the expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the spleen and the development of splenic germinal centers. Furthermore, the transgenic coexpression of the TNFRp55 mutants in TNFRp55(+/-) mice exerts a dominant negative effect on the signaling of the endogenous receptor chains in vivo.