Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University, Düsseldorf, Germany.
Institute of Inflammation and Neurodegeneration, Otto-von-Guericke-University, Magdeburg, Germany.
Infect Immun. 2021 May 17;89(6). doi: 10.1128/IAI.00026-21.
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. -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 infection. Notably, analysis of RNA-seq data clearly indicates a specific effect of 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 .
淋巴毒素 β 受体（LTβR）在引发针对细胞内病原体的免疫反应中起着至关重要的作用。在小鼠中，LTβR 对于急性弓形虫病的存活至关重要；然而，到目前为止，其功能分析在很大程度上并不完整。在这里，我们证明 LTβR 是调节适应性免疫反应复杂平衡的关键调节剂。感染 LTβR 缺陷（LTβR）的小鼠表现出全局改变的干扰素-γ（IFN-γ）调节、减少 IFN-γ 控制的宿主效应分子表达、受损的 T 细胞功能以及不存在针对寄生虫的特异性 IgG 反应，导致对寄生虫的免疫控制严重丧失。用弓形体免疫血清重建 LTβR 小鼠，在感染后显著延长了存活时间。值得注意的是，RNA-seq 数据分析清楚地表明了感染对 B 细胞反应和同种型转换的特定影响。这项研究揭示了 LTβR 在细胞因子调节和适应性免疫反应中的决定性作用，以控制感染。
