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

AbstractThe 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.