Th1/Th17-mediated Immunity and Protection from Peripheral Neuropathy in Wildtype and IL10-/- BALB/c Mice Infected with a Guillain-Barré Syndrome-associated Campylobacter jejuni Strain.

IF 1.3 4区 农林科学 Q2 VETERINARY SCIENCES
Comparative medicine Pub Date : 2022-04-01 Epub Date: 2022-03-10 DOI:10.30802/AALAS-CM-21-000059
Jean M Brudvig, Matthew M Cluett, Elizabeth U Gensterblum-Miller, James Chen, Julia A Bell, Linda S Mansfield
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引用次数: 0

Abstract

Campylobacter jejuni is an important cause of bacterial gastroenteritis worldwide and is linked to Guillain-Barré syndrome (GBS), a debilitating postinfectious polyneuropathy. The immunopathogenesis of GBS involves the generation of antibodies that are cross reactive to C. jejuni lipooligosaccharide and structurally similar peripheral nerve gangliosides. Both the C. jejuni infecting strain and host factors contribute to GBS development. GBS pathogenesis is associated with Th2-mediated responses in patients. Moreover, induction of IgG1 antiganglioside antibodies in association with colonic Th2-mediated immune responses has been reported in C. jejuni-infected C57BL/6 IL10-/- mice at 4 to 6 wk after infection. We hypothesized that, due to their Th2 immunologic bias, BALB/c mice would develop autoantibodies and signs of peripheral neuropathy after infection with a GBS patient-derived strain of C. jejuni (strain 260.94). WT and IL10-/- BALB/c mice were orally inoculated with C. jejuni 260.94, phenotyped weekly for neurologic deficits, and euthanized after 5 wk. Immune responses were assessed as C. jejuni-specific and antiganglioside antibodies in plasma and cytokine production and histologic lesions in the proximal colon. Peripheral nerve lesions were assessed in dorsal root ganglia and their afferent nerve fibers by scoring immunohistochemically labeled macrophages through morphometry. C. jejuni 260.94 stably colonized both WT and IL10-/- mice and induced systemic Th1/Th17-mediated immune responses with significant increases in C. jejuni-specific IgG2a, IgG2b, and IgG3 plasma antibodies. However, C. jejuni 260.94 did not induce IgG1 antiganglioside antibodies, colitis, or neurologic deficits or peripheral nerve lesions in WT or IL10-/- mice. Both WT and IL10-/- BALB/c mice showed relative protection from development of Th2-mediated immunity and antiganglioside antibodies as compared with C57BL/6 IL10-/- mice. Therefore, BALB/c mice infected with C. jejuni 260.94 are not an effective disease model but provide the opportunity to study the role of immune mechanisms and host genetic background in the susceptibility to post infectious GBS.

野生型和IL10-/- BALB/c小鼠感染格林-巴勒综合征相关空肠弯曲杆菌株时,Th1/ th17介导的免疫和周围神经病变的保护作用
空肠弯曲杆菌是全球细菌性肠胃炎的重要原因,与格林-巴利综合征(GBS)有关,后者是一种使人衰弱的感染后多发性神经病。GBS的免疫发病机制涉及产生对空肠弯曲菌脂寡糖和结构相似的外周神经神经节苷脂具有交叉反应性的抗体。空肠弯曲菌感染菌株和宿主因子都有助于GBS的发展。GBS的发病机制与患者Th2介导的反应有关。此外,据报道,在感染后4至6周,在空肠弯曲菌感染的C57BL/6 IL10-/-小鼠中诱导与结肠Th2介导的免疫反应相关的IgG1抗神经节苷脂抗体。我们假设,由于其Th2免疫偏向,BALB/c小鼠在感染GBS患者来源的空肠弯曲菌菌株(菌株260.94)后会出现自身抗体和周围神经病变迹象。WT和IL10-/-BALB/c鼠口服空肠弯曲菌260.94,每周进行神经缺陷表型分型,并在5周后实施安乐死。免疫反应评估为血浆中的空肠弯曲菌特异性抗体和抗神经节苷脂抗体,以及近端结肠的细胞因子产生和组织学损伤。通过形态计量学对免疫组织化学标记的巨噬细胞进行评分,评估背根神经节及其传入神经纤维的周围神经损伤。空肠弯曲杆菌260.94稳定地定殖WT和IL10-/-小鼠,并诱导全身Th1/Th17介导的免疫反应,空肠弯曲杆菌特异性IgG2a、IgG2b和IgG3血浆抗体显著增加。然而,空肠弯曲菌260.94在WT或IL10-/-小鼠中未诱导IgG1抗神经节苷脂抗体、结肠炎、神经功能缺损或外周神经损伤。与C57BL/6 IL10-/-小鼠相比,WT和IL10-/-BALB/c小鼠对Th2介导的免疫和抗神经节苷脂抗体的产生都表现出相对的保护作用。因此,感染空肠弯曲菌260.94的BALB/c小鼠不是一种有效的疾病模型,但为研究免疫机制和宿主遗传背景在感染后GBS易感性中的作用提供了机会。
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来源期刊
Comparative medicine
Comparative medicine 医学-动物学
CiteScore
1.90
自引率
0.00%
发文量
71
审稿时长
6-12 weeks
期刊介绍: Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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