当前位置: X-MOL 学术Virulence › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Relevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice.
Virulence ( IF 5.2 ) Pub Date : 2020-05-14 , DOI: 10.1080/21505594.2020.1763055
Ketema Abdissa 1, 2 , Nanthapon Ruangkiattikul 1 , Wiebke Ahrend 1 , Andreas Nerlich 1 , Andreas Beineke 3 , Kristin Laarmann 1 , Nina Janze 1 , Ulrike Lobermeyer 4 , Abdulhadi Suwandi 2 , Christine Falk 5 , Ulrike Schleicher 6 , Siegfried Weiss 2, 7 , Christian Bogdan 6 , Ralph Goethe 1
Affiliation  

Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease (JD), an incurable chronic intestinal bowel disease in ruminants. JD occurs worldwide and causes enormous economic burden in dairy industry. Research on JD pathobiology is hampered by its complexity which cannot completely be mimicked by small animal models. As a model the mouse allows dissecting some pathogenicity features of MAP. However, for unknown reasons MAP exhibits reduced growth in granulomas of infected mice compared to other Mycobacterium avium subspecies. Here, we characterized immune reactions of MAP-infected C57BL/6 mice. After infection, mice appeared fully immunocompetent. A strong antigen-specific T cell response was elicited indicated by IFNγ production of splenic T cells re-stimulated with MAP antigens. Function of splenic dendritic cells and proliferation of adoptively transferred antigen-specific CD4+ T cells was unaltered. Isolated splenic myeloid cells from infected mice revealed that MAP resides in CD11b+ macrophages. Importantly, sorted CD11b+CD11c- cells expressed high level of type 2 nitric oxide synthase (NOS2) but only low levels of pro- and anti-inflammatory cytokines. Correspondingly, MAP-infected MAC2 expressing myeloid cells in spleen and liver granuloma displayed strong expression of NOS2. In livers of infected Nos2-/-mice higher bacterial loads, more granuloma and larger areas of tissue damage were observed 5 weeks post infection compared to wild type mice. In vitro, MAP was sensitive to NO released by a NO-donor. Thus, a strong T cell response and concomitant NOS2/NO activity appears to control MAP infection, but allows development of chronicity and pathogen persistence. A similar mechanism might explain persistence of MAP in ruminants.

中文翻译:

诱导型一氧化氮合酶对小鼠鸟分枝杆菌亚种副结核感染的免疫控制的相关性。

禽分枝杆菌亚种副结核病(MAP)引起约翰尼氏病(JD),这是反刍动物中一种无法治愈的慢性肠道肠病。京东发生在世界各地,给乳制品行业造成巨大的经济负担。JD病理生物学的研究因其复杂性而受到阻碍,而小型动物模型无法完全模仿它。作为模型,小鼠可以解剖MAP的某些致病性特征。但是,由于未知原因,与其他鸟分枝杆菌亚种相比,MAP在受感染小鼠肉芽肿中的生长减少。在这里,我们表征了MAP感染的C57BL / 6小鼠的免疫反应。感染后,小鼠表现出完全的免疫能力。通过用MAP抗原重新刺激的脾脏T细胞的IFNγ产生,引起了强烈的抗原特异性T细胞应答。脾树突状细胞的功能和过继转移的抗原特异性CD4 + T细胞的增殖未改变。从受感染小鼠中分离出的脾髓样细胞显示,MAP位于CD11b +巨噬细胞中。重要的是,分类的CD11b + CD11c-细胞表达高水平的2型一氧化氮合酶(NOS2),但仅表达低水平的促炎和抗炎细胞因子。相应地,脾和肝肉芽肿中MAP感染的表达MAC2的髓样细胞显示出NOS2的强表达。与野生型小鼠相比,感染Nos2-/-小鼠的肝脏在感染后5周观察到较高的细菌载量,更多的肉芽肿和更大的组织损伤区域。在体外,MAP对NO供体释放的NO敏感。因此,强烈的T细胞反应和伴随的NOS2 / NO活性似乎可以控制MAP感染,但可以发展为慢性和病原体。类似的机制可能解释了反刍动物中MAP的持久性。
更新日期:2020-05-14
down
wechat
bug