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Lymphotoxin β Receptor: a Crucial Role in Innate and Adaptive Immune Responses against Toxoplasma gondii
Author(s) -
Anne Tersteegen,
Ursula R. Sorg,
Richard Virgen-Slane,
Marcel Helle,
Patrick Petzsch,
Ildikò Rita Dunay,
Karl Köhrer,
Daniel Degrandi,
Carl F. Ware,
Klaus Pfeffer
Publication year - 2021
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00026-21
Subject(s) - lymphotoxin , biology , toxoplasma gondii , immune system , immunology , innate immune system , acquired immune system , toxoplasmosis , lymphotoxin beta receptor , virology , receptor , lymphotoxin alpha , intracellular parasite , antibody , biochemistry
The lymphotoxin β receptor (LTβR) plays an essential role in the initiation of immune responses to intracellular pathogens. In mice, the LTβR is crucial for surviving acute toxoplasmosis; however, until now, a functional analysis was largely incomplete. Here, we demonstrate that the LTβR is a key regulator required for the intricate balance of adaptive immune responses. Toxoplasma gondii -infected LTβR-deficient (LTβR -/- ) mice show globally altered interferon-γ (IFN-γ) regulation, reduced IFN-γ-controlled host effector molecule expression, impaired T cell functionality, and an absent anti-parasite-specific IgG response, resulting in a severe loss of immune control of the parasites. Reconstitution of LTβR -/- mice with toxoplasma immune serum significantly prolongs survival following T. gondii infection. Notably, analysis of RNA-seq data clearly indicates a specific effect of T. gondii infection on the B cell response and isotype switching. This study uncovers the decisive role of the LTβR in cytokine regulation and adaptive immune responses to control T. gondii .

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