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

Autor:	Tersteegen A; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University, Düsseldorf, Germany.; Institute of Inflammation and Neurodegeneration, Otto-von-Guericke-University, Magdeburg, Germany., Sorg UR; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University, Düsseldorf, Germany., Virgen-Slane R; Laboratory of Molecular Immunology, Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA., Helle M; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University, Düsseldorf, Germany., Petzsch P; Biological and Medical Research Center (BMFZ), Heinrich Heine University, Düsseldorf, Germany., Dunay IR; Institute of Inflammation and Neurodegeneration, Otto-von-Guericke-University, Magdeburg, Germany., Köhrer K; Biological and Medical Research Center (BMFZ), Heinrich Heine University, Düsseldorf, Germany., Degrandi D; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University, Düsseldorf, Germany., Ware CF; Laboratory of Molecular Immunology, Infectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA., Pfeffer K; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University, Düsseldorf, Germany klaus.pfeffer@hhu.de.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2021 May 17; Vol. 89 (6). Date of Electronic Publication: 2021 May 17 (Print Publication: 2021).
DOI:	10.1128/IAI.00026-21
Abstrakt:	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.)
Databáze:	MEDLINE
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