Lymphotoxin β receptor: A crucial role in innate and adaptive immune responses against Toxoplasma gondii

Tersteegen, A. K.; Sorg, U. R.; Virgen-Slane, R.; Helle, M.; Petzsch, P.; Dunay, I. R.; Köhrer, K.; Degrandi, D.; Ware, C. F.; Pfeffer, K.

doi:10.1101/2021.01.11.426315

bioRxiv · 10.1101/2021.01.11.426315

Lymphotoxin β receptor: A crucial role in innate and adaptive immune responses against Toxoplasma gondii

Tersteegen, A. K.·Sorg, U. R.·Virgen-Slane, R.·Helle, M.·Petzsch, P.·Dunay, I. R.·Köhrer, K.·Degrandi, D.·Ware, C. F.·Pfeffer, K.

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Abstract

The LT{beta}R plays an essential role in the initiation of immune responses to intracellular pathogens. In mice, the LT{beta}R is crucial for surviving acute toxoplasmosis, however, up to now a functional analysis is largely incomplete. Here, we demonstrate that the LT{beta}R is a key regulator required for the intricate balance of adaptive immune responses. T. gondii infected LT{beta}R-/- mice show globally altered IFN{gamma} regulation, reduced IFN{gamma}-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 LT{beta}R-/- mice with toxoplasma immune serum significantly prolongs the survival following T. gondii infection. Notably, analysis of RNAseq data clearly indicates a specific effect of T. gondii infection on the B cell response and isotype switching. This study unfolds the decisive role of the LT{beta}R in cytokine regulation and adaptive immune responses to control T. gondii.

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Tersteegen, A. K., Sorg, U. R., Virgen-Slane, R., Helle, M., Petzsch, P., Dunay, I. R., Köhrer, K., Degrandi, D., Ware, C. F., Pfeffer, K.. 2021-01-14. Lymphotoxin β receptor: A crucial role in innate and adaptive immune responses against Toxoplasma gondii. https://doi.org/10.1101/2021.01.11.426315

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