Lymphotoxin β Receptor: a Crucial Role in Innate and Adaptive Immune Responses against Toxoplasma gondii.

Anne Tersteegen, Ursula R Sorg, Richard Virgen-Slane, Marcel Helle, Patrick Petzsch, Ildiko R Dunay, Karl Köhrer, Daniel Degrandi, Carl F Ware, Klaus Pfeffer

Infection and immunity 2021 May 17

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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. Copyright © 2021 Tersteegen et al.

Citation

Anne Tersteegen, Ursula R Sorg, Richard Virgen-Slane, Marcel Helle, Patrick Petzsch, Ildiko R Dunay, Karl Köhrer, Daniel Degrandi, Carl F Ware, Klaus Pfeffer. Lymphotoxin β Receptor: a Crucial Role in Innate and Adaptive Immune Responses against Toxoplasma gondii. Infection and immunity. 2021 May 17;89(6)