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首页> 外文期刊>Infection and immunity >Phosphoinositide 3-Kinase-Dependent Inhibition of Dendritic Cell Interleukin-12 Production by Giardia lamblia
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Phosphoinositide 3-Kinase-Dependent Inhibition of Dendritic Cell Interleukin-12 Production by Giardia lamblia

机译：贾第鞭毛虫对树突状细胞白细胞介素12产生的磷酸肌醇3-激酶依赖性抑制。

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Dendritic cell interactions with pathogenic microbes initiate and direct the development of subsequent adaptive responses. The protozoan pathogen Giardia lamblia infects the mammalian small intestine, leading to nutrient malabsorption and diarrhea but rarely causing inflammation. In order to begin to understand how the innate immune system responds to this parasite and shapes the eventual adaptive response, we examined the interaction between parasites and murine bone marrow-derived dendritic cells (DCs). DCs incubated with live parasites or parasite extracts displayed enhanced levels of CD40. The expression of CD80 and CD86 also increased, but less than was seen with lipopolysaccharide-activated DCs. Small amounts of interleukin-6 (IL-6) and tumor necrosis factor alpha were secreted by these DCs, whereas no IL-10 or IL-12 could be detected. Coincubation of DCs with parasite extracts along with known Toll-like receptor (TLR) ligands resulted in enhanced secretion of IL-10 and reduced secretion of IL-12. The levels of major histocompatibility complex class II, CD80, and CD86 were also reduced compared to DCs stimulated with TLR ligands alone. Finally, studies with an extracellular signal-regulated kinase 1/2 pathway inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, and anti-IL-10 receptor antibody revealed that the PI3K pathway is the dominant mechanism of inhibition in DCs incubated with both lipopolysaccharide and Giardia. These data suggest that this parasite actively interferes with host innate immunity, resulting in an immune response able to control the infection but devoid of strong inflammatory signals.
机译：树突状细胞与病原微生物的相互作用引发并指导随后的适应性反应的发展。原生动物病原菌 Giardia lamblia 感染哺乳动物的小肠，导致营养吸收不良和腹泻，但很少引起炎症。为了开始了解先天免疫系统如何响应此寄生虫并塑造最终的适应性反应，我们研究了寄生虫与鼠骨髓来源的树突状细胞（DC）之间的相互作用。与活的寄生虫或寄生虫提取物孵育的DC表现出增强的CD40水平。 CD80和CD86的表达也增加了，但比脂多糖激活的DC少。这些DC分泌少量白细胞介素6（IL-6）和肿瘤坏死因子α，而未检测到IL-10或IL-12。将DC与寄生虫提取物以及已知的Toll样受体（TLR）配体共孵育会导致IL-10分泌增加和IL-12分泌减少。与单独用TLR配体刺激的DC相比，II型主要组织相容性复合物CD80和CD86的水平也降低了。最后，对细胞外信号调节激酶1/2途径抑制剂，磷酸肌醇3激酶（PI3K）抑制剂和抗IL-10受体抗体的研究表明，PI3K途径是在与二者孵育的DC中抑制作用的主要机制脂多糖和 Giardia 。这些数据表明，这种寄生虫会主动干扰宿主的先天免疫，从而导致能够控制感染但没有强烈炎症信号的免疫反应。

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