内源性先天性传感器 NLRP3 是腹腔巨噬细胞动态的关键组成部分,是绦虫建立所必需的。

IF 3.3 4区 医学 Q3 IMMUNOLOGY
Immunologic Research Pub Date : 2024-10-01 Epub Date: 2024-06-06 DOI:10.1007/s12026-024-09496-3
Irán Flores-Sotelo, Natalia Juárez, Marisol I González, Auraamellaly Chávez, Danielle T Vannan, Bertus Eksteen, Luis I Terrazas, José L Reyes
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引用次数: 0

摘要

NLRP3 受体可以组装炎症小体平台,引发炎症反应;然而,越来越多的证据表明,它也可以表现出抗炎特性。在这里,我们探讨了核苷酸结合寡聚化结构域含吡喃蛋白 3(NLRP3)在克氏疟原虫实验性感染中的作用,这种感染需要免疫极化为 Th2 型特征和腹腔抑制性巨噬细胞的涌入才能成功定殖。与野生型(WT)小鼠相比,缺乏 NLRP3 的小鼠(NLRP3-/-)对 T. crassiceps 有很强的抵抗力。NLRP3-/-小鼠的抵抗力与IL-4输出量减少、先天性和适应性淋巴细胞生长因子IL-15水平升高以及腹膜浸润抑制性巨噬细胞急剧减少有关。此外,对暴露于洮螨分泌的抗原和 IL-4 的骨髓巨噬细胞进行的转录分析表明,NLRP3-/-巨噬细胞表达的 relm-α 和 PD-1 配体的转录本减少,而这两种配体分别是替代活化和抑制能力的标志。最后,我们发现 NLRP3-/- 小鼠表现出的抵抗力是通过肠道微生物群交换传递的,因为与 NLRP3-/- 小鼠共处一室的 WT 小鼠的抵抗力明显高于保留其本地微生物群的 WT 动物。总之,这些数据证明了 NLRP3 是 T. crassiceps 建立所需的先天性免疫的一个组成部分,很可能有助于巨噬细胞的招募,并控制淋巴细胞刺激细胞因子(如 IL-15)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Endogenous innate sensor NLRP3 is a key component in peritoneal macrophage dynamics required for cestode establishment.

Endogenous innate sensor NLRP3 is a key component in peritoneal macrophage dynamics required for cestode establishment.

The NLRP3 receptor can assemble inflammasome platforms to trigger inflammatory responses; however, accumulating evidence suggests that it can also display anti-inflammatory properties. Here, we explored the role of nucleotide-binding oligomerization domain pyrin-containing protein 3 (NLRP3) in Taenia crassiceps experimental infection, which requires immune polarization into a Th2-type profile and peritoneal influx of suppressive macrophages for successful colonization. NLRP3 deficient mice (NLRP3-/-) were highly resistant against T. crassiceps, relative to wild-type (WT) mice. Resistance in NLRP3-/- mice was associated with a diminished IL-4 output, high levels of IL-15, growth factor for both innate and adaptive lymphocytes, and a dramatic decrease in peritoneum-infiltrating suppressive macrophages. Also, a transcriptional analysis on bone marrow-derived macrophages exposed to Taenia-secreted antigens and IL-4 revealed that NLRP3-/- macrophages express reduced transcripts of relm-α and PD-1 ligands, markers of alternative activation and suppressive ability, respectively. Finally, we found that the resistance displayed by NLRP3-/- mice is transferred through intestinal microbiota exchange, since WT mice co-housed with NLRP3-/- mice were significantly more resistant than WT animals preserving their native microbiota. Altogether, these data demonstrate that NLRP3 is a component of innate immunity required for T. crassiceps to establish, most likely contributing to macrophage recruitment, and controlling lymphocyte-stimulating cytokines such as IL-15.

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来源期刊
Immunologic Research
Immunologic Research 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
83
审稿时长
6-12 weeks
期刊介绍: IMMUNOLOGIC RESEARCH represents a unique medium for the presentation, interpretation, and clarification of complex scientific data. Information is presented in the form of interpretive synthesis reviews, original research articles, symposia, editorials, and theoretical essays. The scope of coverage extends to cellular immunology, immunogenetics, molecular and structural immunology, immunoregulation and autoimmunity, immunopathology, tumor immunology, host defense and microbial immunity, including viral immunology, immunohematology, mucosal immunity, complement, transplantation immunology, clinical immunology, neuroimmunology, immunoendocrinology, immunotoxicology, translational immunology, and history of immunology.
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