Immunomodulatory parasites and toll-like receptor-mediated tumour necrosis factor alpha responsiveness in wild mammals.
Immunomodulatory parasites and toll-like receptor-mediated tumour necrosis factor alpha responsiveness in wild mammals.
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DOI：
10.1186/1741-7007-7-16
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发表时间：
2009-04-22
期刊：
影响因子：
5.4
通讯作者：
Bradley JE
中科院分区：
文献类型：
--
作者：
Jackson JA;Friberg IM;Bolch L;Lowe A;Ralli C;Harris PD;Behnke JM;Bradley JE
对野生种群的免疫学分析可以增加我们对脊椎动物免疫系统如何对不同感染的“自然”暴露水平作出反应的理解。最近免疫学的一个重大进展是认识到遗传上保守的toll样受体在触发先天免疫和随后的适应性反应程序的募集中的中心作用。我们研究了自然木鼠（森林姬鼠）种群中系统性Toll样受体介导的肿瘤坏死因子α反应性和大型和微型寄生虫感染的个体水平之间的横截面关联。在一组不同的大型寄生虫中，只有线虫Heligmosomoides polygyrus和虱子Polyplax serrata的水平与先天性免疫反应（通过脾细胞肿瘤坏死因子α对一组Toll样受体激动剂的反应来测量）相关（负相关）。锯缘多膜虫感染解释了先天反应总变异的一个惊人的高比例。相比之下，微寄生艾美耳球虫属的粪便卵囊计数。与先天性免疫反应性正相关，对于内体受体TLR7和TLR9最显著。与相关实验室模型的类比表明，所观察到的模式的潜在因果关系可能是寄生虫驱动的对宿主的免疫调节作用。免疫调节寄生虫物种的一个子集，因此可以有一个关键的作用，通过影响“上游”的先天介质，如收费样受体，这是重要的启动免疫在自然脊椎动物种群的其他感染结构。此外，本研究结果的幅度表明，无免疫抑制寄生虫的人群可能存在先天免疫激活的“非自然”升高水平，可能导致免疫病理学风险增加。
Immunological analyses of wild populations can increase our understanding of how vertebrate immune systems respond to 'natural' levels of exposure to diverse infections. A major recent advance in immunology has been the recognition of the central role of phylogenetically conserved toll-like receptors in triggering innate immunity and the subsequent recruitment of adaptive response programmes. We studied the cross-sectional associations between individual levels of systemic toll-like receptor-mediated tumour necrosis factor alpha responsiveness and macro- and microparasite infections in a natural wood mouse (Apodemus sylvaticus) population. Amongst a diverse group of macroparasites, only levels of the nematode Heligmosomoides polygyrus and the louse Polyplax serrata were correlated (negatively) with innate immune responsiveness (measured by splenocyte tumour necrosis factor alpha responses to a panel of toll-like receptor agonists). Polyplax serrata infection explained a strikingly high proportion of the total variation in innate responses. Contrastingly, faecal oocyst count in microparasitic Eimeria spp. was positively associated with innate immune responsiveness, most significantly for the endosomal receptors TLR7 and TLR9. Analogy with relevant laboratory models suggests the underlying causality for the observed patterns may be parasite-driven immunomodulatory effects on the host. A subset of immunomodulatory parasite species could thus have a key role in structuring other infections in natural vertebrate populations by affecting the 'upstream' innate mediators, like toll-like receptors, that are important in initiating immunity. Furthermore, the magnitude of the present result suggests that populations free from immunosuppressive parasites may exist at 'unnaturally' elevated levels of innate immune activation, perhaps leading to an increased risk of immunopathology.
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影响因子：
5.4
作者：
Finney, Constance A M;Taylor, Matthew D;Wilson, Mark S;Maizels, Rick M
通讯作者：
Maizels, Rick M
影响因子：
5.7
作者：
Ferwerda, Bart;McCall, Matthew B. B.;Netea, Mihai G.
通讯作者：
Netea, Mihai G.
影响因子：
3.8
作者：
Bochud, Pierre-Yves;Hersberger, Martin;Aderem, Alan
通讯作者：
Aderem, Alan
影响因子：
2.8
作者：
Deviche, P;Cortez, L
通讯作者：
Cortez, L
DOI：
10.1073/pnas.0707221105
发表时间：
2008-01-15
影响因子：
11.1
作者：
Graham, Andrea L.
通讯作者：
Graham, Andrea L.