Linnemann Lara, Antwi-Ekwuruke Jennifer, Gnanapragassam Vinayaga, Bang Corinna, Rühlemann Malte, Ruland Jürgen, Hartmann Wiebke, Heepmann Lennart, Dörken Sara, Yunus Saleh M, Viebrock Birte, Schlosser Annette, Lepenies Bernd, Breloer Minka
Section Interface, Bernhard Nocht Institute for Tropical Medicine, 20359, Hamburg, Germany.
Institute for Immunology, University of Veterinary Medicine Hannover, 30559, Hanover, Germany; Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, 30559, Hanover, Germany.
Mucosal Immunol. 2025 Feb;18(1):220-231. doi: 10.1016/j.mucimm.2024.11.005. Epub 2024 Nov 22.
Strongyloides ratti is a helminth parasite that displays tissue-migrating and intestinal life stages. Myeloid C-type lectin receptors (CLRs) are pattern recognition receptors that recognize pathogen-derived ligands and initiate immune responses. To date, the role of CLRs in S. ratti infection has not been investigated. Here, we show that S. ratti-derived ligands are recognized by the CLR Macrophage inducible Ca-dependent lectin receptor (MINCLE). While MINCLE-deficiency did not affect initiation of a protective anti-S. ratti type 2 immunity, MINCLE-deficient mice had a transient advantage in intestinal immunity. Unravelling the underlying mechanism, we show that next to macrophages, dendritic cells and neutrophils, a fraction of eosinophils express MINCLE and expand during S. ratti infection. MINCLE-deficient eosinophils exhibited a more active phenotype and prolonged expansion in vivo and displayed increased capacity to reduce S. ratti motility and produce reactive oxygen species in vitro, compared to wild-type (WT) eosinophils. Depletion of eosinophils in S. ratti-infected mice after the tissue-migration phase elevated intestinal worm burden in MINCLE-deficient mice to the WT level. Thus, our findings establish a central contribution of eosinophils to parasite ejection from the intestine and suggest that S. ratti-triggered signalling via MINCLE interferes with eosinophil mediated ejection of S. ratti from the intestine.
大鼠类圆线虫是一种表现出组织迁移和肠道生活阶段的蠕虫寄生虫。髓样C型凝集素受体（CLRs）是识别病原体衍生配体并启动免疫反应的模式识别受体。迄今为止，尚未研究CLRs在大鼠类圆线虫感染中的作用。在此，我们表明大鼠类圆线虫衍生的配体可被CLR巨噬细胞诱导的钙依赖性凝集素受体（MINCLE）识别。虽然MINCLE缺陷并不影响保护性抗大鼠类圆线虫2型免疫的启动，但MINCLE缺陷小鼠在肠道免疫方面具有短暂优势。在揭示其潜在机制时，我们发现除了巨噬细胞、树突状细胞和中性粒细胞外，一部分嗜酸性粒细胞也表达MINCLE，并在大鼠类圆线虫感染期间扩增。与野生型（WT）嗜酸性粒细胞相比，MINCLE缺陷的嗜酸性粒细胞在体内表现出更活跃的表型和更长时间的扩增，并且在体外显示出更强的降低大鼠类圆线虫活力和产生活性氧的能力。在组织迁移阶段后，对感染大鼠类圆线虫的小鼠进行嗜酸性粒细胞清除，可使MINCLE缺陷小鼠的肠道蠕虫负担升高至WT水平。因此，我们的研究结果确立了嗜酸性粒细胞对寄生虫从肠道排出的核心作用，并表明大鼠类圆线虫通过MINCLE触发的信号传导会干扰嗜酸性粒细胞介导的大鼠类圆线虫从肠道的排出。
