Lymphotoxin β Receptor: a Crucial Role in Innate and Adaptive Immune Responses against Toxoplasma gondii.
Lymphotoxin β Receptor: a Crucial Role in Innate and Adaptive Immune Responses against Toxoplasma gondii.
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DOI：
10.1128/iai.00026-21
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发表时间：
2021-05-17
影响因子：
3.1
通讯作者：
Pfeffer K
中科院分区：
文献类型：
--
作者：
Tersteegen A;Sorg UR;Virgen-Slane R;Helle M;Petzsch P;Dunay IR;Köhrer K;Degrandi D;Ware CF;Pfeffer K
淋巴毒素β受体(LTβR)在启动对细胞内病原体的免疫反应中起重要作用。在小鼠中，LTβR对于急性弓形虫病的生存至关重要；然而，到目前为止，功能分析基本上是不完整的。在这里，我们证明LTβR是适应性免疫反应复杂平衡所需的关键调节因子。弓形虫感染的LTβR缺陷(LTβR−/−)小鼠表现出干扰素-γ(干扰素-γ)调节的全局改变，干扰素-γ控制的宿主效应分子表达减少，T细胞功能受损，缺乏抗寄生虫特异性免疫球蛋白应答，导致对寄生虫的严重免疫控制。用弓形虫免疫血清重建LTβR−/−小鼠可显著延长弓形虫感染后的存活时间。值得注意的是，对RNA-seq数据的分析清楚地表明弓形虫感染对B细胞反应和同型转换的特定影响。本研究揭示了LTβR在控制弓形虫的细胞因子调节和获得性免疫反应中的决定性作用。
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.