A Lower Dose of Infection Generates a Better Long-Term Immune Response against Toxoplasma gondii.
A Lower Dose of Infection Generates a Better Long-Term Immune Response against Toxoplasma gondii.
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DOI：
10.4049/immunohorizons.2300006
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发表时间：
2023-02-01
期刊：
影响因子：
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通讯作者：
Khan IA
中科院分区：
文献类型：
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作者：
Moretto MM;Chen J;Meador M;Phan J;Khan IA
弓形虫是一种专性胞内病原体，在感染的宿主中诱导强烈的免疫应答。在脑炎感染模型中，长期保护性免疫由CD 8 T细胞介导，CD 4 T细胞群提供重要帮助。大多数免疫研究使用了10到20个囊肿剂量的T。弓形虫，这导致T细胞功能障碍，在慢性感染的后期阶段，并增加重新激活的机会。在目前的研究中，我们比较了口服感染2个或10个弓形虫包囊的小鼠的免疫应答。刚地。在急性期，我们证明了较低剂量的感染产生的CD 4和CD 8 T细胞数量减少，但功能性CD 4或CD 8 T细胞的频率在两种不同剂量感染的动物中相似。然而，Ag-经验丰富的T细胞（CD 4和CD 8）更好地维持在较低剂量感染的小鼠在8周感染后，与功能细胞的数量增加，表现出较低的多抑制受体表达。除了更好的长期T细胞免疫外，用较低剂量感染的动物在急性感染的非常早期阶段表现出较少的Ag特异性T细胞和细胞因子应答，从而减少炎症。我们的研究表明，剂量依赖性的早期编程/长期的CD 4/CD 8 T细胞反应的T细胞在T细胞免疫过程中的印记以前未被重视的作用。弓形虫感染这些观察结果表明，需要深入分析早期事件如何形成对这种病原体的长期免疫力。
Toxoplasma gondii, an obligate intracellular pathogen, induces a strong immune response in the infected host. In the encephalitis model of infection, long-term protective immunity is mediated by CD8 T cells, with the CD4 T cell population providing important help. Most of the immune studies have used a 10- to 20-cyst dose of T. gondii, which leads to T cell dysfunctionality during the late phase of chronic infection and increases the chances of reactivation. In the current study, we compared the immune response of mice orally infected with either 2 or 10 cysts of T. gondii. During the acute phase, we demonstrate that the lower dose of infection generates a reduced number of CD4 and CD8 T cells, but the frequency of functional CD4 or CD8 T cells is similar in animals infected with two different doses. However, Ag-experienced T cells (both CD4 and CD8) are better maintained in lower dose–infected mice at 8 wk postinfection, with an increase number functional cells that exhibit lower multiple inhibitory receptor expression. In addition to better long-term T cell immunity, animals infected with a lower dose display reduced inflammation manifested by lesser Ag-specific T cell and cytokine responses during the very early stage of the acute infection. Our studies suggest a previously unappreciated role of dose-dependent early programming/imprinting of the long-term CD4/CD8 T cell response during T. gondii infection. These observations point to the need for an in-depth analysis of how early events shape long-term immunity against this pathogen.