Institute of Molecular Medicine, Department of Cardiovascular and Renal Research, University of Southern Denmark, DK-5000 Odense, Denmark.
Institute of Molecular Medicine, Department of Cardiovascular and Renal Research, University of Southern Denmark, DK-5000 Odense, Denmark.
Immunobiology. 2014 Mar;219(3):179-88. doi: 10.1016/j.imbio.2013.10.003. Epub 2013 Oct 12.
Chitin and β-glucan are conserved throughout evolution in the fungal cell wall and are the most common polysaccharides in fungal species. Together, these two polysaccharides form a structural scaffold that is essential for the survival of the fungus. In the present study, we demonstrated that Aspergillus fumigatus alkali-insoluble cell wall fragments (AIF), composed of chitin linked covalently to β-glucan, induced enhanced immune responses when compared with individual cell wall polysaccharides. Intranasal administration of AIF induced eosinophil and neutrophil recruitment, chitinase activity, TNF-α and TSLP production in mice lungs. Selective destruction of chitin or β-glucan from AIF significantly reduced eosinophil and neutrophil recruitment as well as chitinase activity and cytokine expression by macrophages, indicating the synergistic effect of the cell wall polysaccharides when presented together as a composite PAMP. We also showed that these cell wall polysaccharides induced chitin-specific IgM in mouse serum. Our in vivo and in vitro data indicate that chitin and β-glucan play important roles in activating innate immunity when presented as composite cell wall PAMPs.
几丁质和β-葡聚糖在真菌细胞壁中是保守的，是真菌物种中最常见的多糖。这两种多糖共同构成了一个结构支架，对真菌的生存至关重要。在本研究中，我们证明了烟曲霉碱不溶性细胞壁片段（AIF），由共价连接的几丁质和β-葡聚糖组成，与单个细胞壁多糖相比，诱导了增强的免疫反应。AIF 的鼻内给药诱导了嗜酸性粒细胞和中性粒细胞的募集，以及小鼠肺部的几丁质酶活性、TNF-α 和 TSLP 的产生。AIF 中几丁质或β-葡聚糖的选择性破坏显著减少了嗜酸性粒细胞和中性粒细胞的募集以及巨噬细胞的几丁质酶活性和细胞因子表达，表明当作为复合 PAMP 一起呈现时，细胞壁多糖具有协同作用。我们还表明，这些细胞壁多糖在小鼠血清中诱导了几丁质特异性 IgM。我们的体内和体外数据表明，当作为复合细胞壁 PAMP 呈现时，几丁质和β-葡聚糖在激活固有免疫中发挥重要作用。
