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Mediators of Inflammation
Volume 2017 (2017), Article ID 7375818, 16 pages
Research Article

The Lymphotoxin β Receptor Is Essential for Upregulation of IFN-Induced Guanylate-Binding Proteins and Survival after Toxoplasma gondii Infection

1Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany
2Molecular Medicine II, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany
3Institute of Pathology, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany

Correspondence should be addressed to Klaus Pfeffer

Received 14 February 2017; Revised 23 May 2017; Accepted 7 June 2017; Published 6 August 2017

Academic Editor: Célia M. A. Soares

Copyright © 2017 Kristina Behnke et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Lymphotoxin β receptor (LTβR) signaling plays an important role in efficient initiation of host responses to a variety of pathogens, encompassing viruses, bacteria, and protozoans via induction of the type I interferon response. The present study reveals that after Toxoplasma gondii infection, LTβR−/− mice show a substantially reduced survival rate when compared to wild-type mice. LTβR−/− mice exhibit an increased parasite load and a more pronounced organ pathology. Also, a delayed increase of serum IL-12p40 and a failure of the protective IFNγ response in LTβR−/− mice were observed. Serum NO levels in LTβR−/− animals rose later and were markedly decreased compared to wild-type animals. At the transcriptional level, LTβR−/− animals exhibited a deregulated expression profile of several cytokines known to play a role in activation of innate immunity in T. gondii infection. Importantly, expression of the IFNγ-regulated murine guanylate-binding protein (mGBP) genes was virtually absent in the lungs of LTβR−/− mice. This demonstrates clearly that the LTβR is essential for the induction of a type II IFN-mediated immune response against T. gondii. The pronounced inability to effectively upregulate host defense effector molecules such as GBPs explains the high mortality rates of LTβR−/− animals after T. gondii infection.