Department of Microbiology and Immunology, Indiana University School of Medicine-Terre Haute, Terre Haute, IN, United States.
Front Immunol. 2019 May 10;10:1057. doi: 10.3389/fimmu.2019.01057. eCollection 2019.
Chitin is a structural biopolymer found in numerous organisms, including pathogenic fungi, and recognized as an immune-stimulating pathogen associated molecular pattern by pattern recognition molecules of the host immune system. However, programming and regulation of lung innate immunity to chitin inhalation in the context of inhalation of fungal pathogens such as is complex and our understanding incomplete. Here we report that the systemic metabolism-regulating cytokine adiponectin is decreased in the lungs and serum of mice after chitin inhalation, with a concomitant decrease in surface expression of the adiponectin receptor AdipoR1 on lung leukocytes. Constitutive lung expression of acidic mammalian chitinase resulted in decreased inflammatory cytokine gene expression and neutrophil recruitment, but did not significantly affect lung adiponectin transcription. Exogenous recombinant adiponectin specifically dampened airway chitin-mediated eosinophil recruitment, while adiponectin deficiency resulted in increased airway eosinophils. The presence of adiponectin also resulted in decreased CCL11-mediated migration of bone marrow-derived eosinophils. In contrast to purified chitin, aspiration of viable conidia from the high chitin-expressing isolate Af5517 resulted in increased neutrophil recruitment and inflammatory cytokine gene expression in adiponectin-deficient mice, while no significant changes were observed in response to the isolate Af293. Our results identify a novel role for the adiponectin pathway in inhibition of lung inflammatory responses to chitin and inhalation.
几丁质是一种结构生物聚合物，存在于许多生物体中，包括致病性真菌，并被宿主免疫系统的模式识别分子识别为一种免疫刺激的病原体相关分子模式。然而，在吸入真菌病原体（如）的情况下，肺部固有免疫对几丁质吸入的编程和调节是复杂的，我们的理解也不完整。在这里，我们报告称，系统性代谢调节细胞因子脂联素在吸入几丁质后在肺部和血清中的表达降低，同时肺白细胞表面的脂联素受体 AdipoR1 表达也降低。酸性哺乳动物几丁质酶的组成性肺表达导致炎性细胞因子基因表达和中性粒细胞募集减少，但对肺脂联素转录没有显著影响。外源性重组脂联素特异性抑制气道几丁质介导的嗜酸性粒细胞募集，而脂联素缺乏导致气道嗜酸性粒细胞增多。脂联素的存在也导致骨髓衍生嗜酸性粒细胞对 CCL11 介导的迁移减少。与纯化的几丁质不同，从高几丁质表达的 分离株 Af5517 中吸入活孢子会导致脂联素缺陷小鼠中性粒细胞募集和炎性细胞因子基因表达增加，而对分离株 Af293 则没有观察到明显变化。我们的研究结果确定了脂联素途径在抑制肺部对几丁质和 吸入的炎症反应中的新作用。
