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

The 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, up to now a functional analysis is largely incomplete. Here, we demonstrate that the LTβR is a key regulator required for the intricate balance of adaptive immune responses. T. gondii infected LTβR-/- mice show globally altered IFNγ regulation, reduced IFNγ-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 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 LTβR in cytokine regulation and adaptive immune responses to control T. gondii.