缺乏核苷酸寡聚结构域-2的继发性非生物IL-10-/-小鼠空肠弯曲杆菌感染后的小肠促炎免疫反应

European Journal of Microbiology & Immunology Pub Date : 2017-06-27 eCollection Date: 2017-06-01 DOI:10.1556/1886.2017.00005
Markus M Heimesaat, Ursula Grundmann, Marie E Alutis, André Fischer, Stefan Bereswill
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引用次数: 8

摘要

宿主的免疫反应对于对抗包括空肠弯曲杆菌在内的肠致病性感染至关重要。经口空肠梭菌感染后1周内,继发性非生物IL-10-/-小鼠出现严重的影响结肠的免疫病理后遗症(溃疡性小肠结肠炎)。在本研究中,我们研究了病原体诱导的促炎免疫反应是否也可以在小肠中观察到依赖于先天受体核苷酸寡聚结构域蛋白2 (Nod2)。在经口感染后的7天内,空肠梭菌在缺乏Nod2的IL-10-/-小鼠(Nod2-/- IL-10-/-)和IL-10-/-对照组的胃肠道中稳定定植,表现出血性腹泻,频率相似。两种基因型的大肠杆菌感染小鼠的小肠中凋亡和再生上皮细胞数量增加,并伴有回肠T和B淋巴细胞计数升高。值得注意的是,与IL-10-/-相比,肠假梭菌感染Nod2-/- IL-10-/-的回肠T细胞数量更高。此外,在任一基因型的大肠杆菌感染小鼠的小肠离体活检中,均可检测到IFN-γ、TNF和MCP-1等促炎细胞因子浓度的多倍增加。综上所述,空肠梭菌诱导的促炎免疫反应影响了Nod2-/- IL-10-/-和IL-10-/-小鼠的小肠,而前者的回肠T淋巴细胞数量更高。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Small Intestinal Pro-Inflammatory Immune Responses Following Campylobacter Jejuni Infection of Secondary Abiotic IL-10-/- Mice Lacking Nucleotide-Oligomerization-Domain-2.

Host immune responses are crucial for combating enteropathogenic infections including Campylobacter jejuni. Within 1 week following peroral C. jejuni infection, secondary abiotic IL-10-/- mice develop severe immunopathological sequelae affecting the colon (ulcerative enterocolitis). In the present study, we addressed whether pathogen-induced pro-inflammatory immune responses could also be observed in the small intestines dependent on the innate receptor nucleotide-oligomerization-domain-protein 2 (Nod2). Within 7 days following peroral infection, C. jejuni stably colonized the gastrointestinal tract of both IL-10-/- mice lacking Nod2 (Nod2-/- IL-10-/-) and IL-10-/- controls displaying bloody diarrhea with similar frequencies. Numbers of apoptotic and regenerating epithelial cells increased in the small intestines of C. jejuni-infected mice of either genotype that were accompanied by elevated ileal T and B lymphocyte counts. Notably, ileal T cell numbers were higher in C. jejuni-infected Nod2-/- IL-10-/- as compared to IL-10-/- counterparts. Furthermore, multifold increased concentrations of pro-inflammatory cytokines including IFN-γ, TNF, and MCP-1 could be measured in small intestinal ex vivo biopsies derived from C. jejuni-infected mice of either genotype. In conclusion, C. jejuni-induced pro-inflammatory immune responses affected the small intestines of both Nod2-/- IL-10-/- and IL-10-/- mice, whereas ileal T lymphocyte numbers were even higher in the former.

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