Da Silva Carla A, Chalouni Cécile, Williams Adam, Hartl Dominik, Lee Chun G, Elias Jack A
Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06519, USA.
J Immunol. 2009 Mar 15;182(6):3573-82. doi: 10.4049/jimmunol.0802113.
Chitin is a ubiquitous polysaccharide in fungi, insects, and parasites. We hypothesized that chitin is a size-dependent regulator of innate immunity. To test this hypothesis, we characterized the effects of chitins of different sizes on murine bronchoalveolar or peritoneal macrophages. In these studies, large chitin fragments were inert, while both intermediate-sized chitin (40-70 microm) and small chitin (SC; <40 microm, largely 2-10 microm) stimulated TNF elaboration. In contrast, only SC induced IL-10 elaboration. The effects of intermediate-sized chitin were mediated by pathways that involve TLR2, dectin-1, and NF-kappaB. In contrast, the effects of SC were mediated by TLR2-dependent and -independent, dectin-1-dependent pathways that involved the mannose receptor and spleen tyrosine kinase. Chitin contains size-dependent pathogen-associated molecular patterns that stimulate TLR2, dectin-1, and the mannose receptor, differentially activate NF-kappaB and spleen tyrosine kinase, and stimulate the production of pro- and anti-inflammatory cytokines.
几丁质是真菌、昆虫和寄生虫中普遍存在的一种多糖。我们推测几丁质是天然免疫的一种大小依赖性调节因子。为验证这一假设，我们对不同大小的几丁质对小鼠支气管肺泡或腹腔巨噬细胞的影响进行了表征。在这些研究中，大的几丁质片段无活性，而中等大小的几丁质（40 - 70微米）和小的几丁质（SC；<40微米，主要为2 - 10微米）均能刺激肿瘤坏死因子（TNF）的产生。相比之下，只有SC能诱导白细胞介素-10（IL-10）的产生。中等大小几丁质的作用是由涉及Toll样受体2（TLR2）、树突状细胞相关C型凝集素-1（dectin-1）和核因子κB（NF-κB）的信号通路介导的。相比之下，SC的作用是由依赖和不依赖TLR2、依赖dectin-1的信号通路介导的，这些通路涉及甘露糖受体和脾酪氨酸激酶。几丁质含有大小依赖性的病原体相关分子模式，可刺激TLR2、dectin-1和甘露糖受体，差异性激活NF-κB和脾酪氨酸激酶，并刺激促炎和抗炎细胞因子的产生。
