Macroparasites at peripheral sites of infection are major and dynamic modifiers of systemic anti-microbial pattern recognition responses

Immune defences and the maintenance of immunological homeostasis in the face of pathogenic and commensal microbial exposures are channelled by innate anti-microbial pattern recognition receptors (PRRs) such as toll-like receptors (TLRs). Whilst PRR-mediated response programmes are the result of long-term host-pathogen or host-commensal co-evolutionary dynamics involving microbes, an additional possibility is that macroparasitic co-infections may be a significant modifier of such interactions. We demonstrate experimentally that macroparasites (the model gastrointestinal nematode, Heligmosomoides) at peripheral sites of infection cause substantial alteration of the expression and function of TLRs at a systemic level (in cultured splenocytes), predominantly up-regulating TLR2, TLR4 and TLR9-mediated cytokine responses at times of high standing worm burdens. We consistently observed such effects in BALB/c and C57BL/6 mice under single-pulse and trickle exposures to Heligmosomoides larvae an...

面对致病性与共生性微生物暴露时，免疫防御及免疫稳态的维持，由先天抗微生物模式识别受体（pattern recognition receptors, PRRs）（如 toll样受体（toll-like receptors, TLRs））介导。尽管PRR介导的应答程序是微生物参与的宿主-病原体或宿主-共生体长期协同进化动态的结果，但另一种可能性是，宏寄生共感染可能是此类相互作用的重要调节因素。我们通过实验证明，外周感染部位的宏寄生虫（模型胃肠道线虫Heligmosomoides）会在系统水平（培养的脾细胞中）显著改变TLR的表达与功能，尤其在高持续蠕虫负荷时上调TLR2、TLR4及TLR9介导的细胞因子应答。