Allard Jenna B, Rinaldi Lisa, Wargo Matthew J, Allen Gilman, Akira Shizuo, Uematsu Satoshi, Poynter Matthew E, Hogan Deborah A, Rincon Mercedes, Whittaker Laurie A
Department of Medicine, Division of Pulmonary Disease and Critical Care, Vermont Lung Center, University of Vermont, Burlington, VT, USA.
Eur J Immunol. 2009 Mar;39(3):776-88. doi: 10.1002/eji.200838932.
Allergic airway disease is characterized by eosinophilic inflammation, mucus hypersecretion and increased airway resistance. Fungal antigens are ubiquitous within the environment and are well known triggers of allergic disease. Bacterial products are also frequently encountered within the environment and may alter the immune response to certain antigens. The consequence of simultaneous exposure to bacterial and fungal products on the lung adaptive immune response has not been explored. Here, we show that oropharyngeal aspiration of fungal lysates (Candida albicans, Aspergillus fumigatus) promotes airway eosinophilia, secretion of Th2 cytokines and mucus cell metaplasia. In contrast, oropharyngeal exposure to bacterial lysates (Pseudomonas aeruginosa) promotes airway inflammation characterized by neutrophils, Th1 cytokine secretion and no mucus production. More importantly, administration of bacterial lysates together with fungal lysates deviates the adaptive immune response to a Th1 type associated with neutrophilia and diminished mucus production. The immunomodulatory effect that bacterial lysates have on the response to fungi is TLR4 independent but MyD88 dependent. Thus, different types of microbial products within the airway can alter the host's adaptive immune response and potentially impact the development of allergic airway disease to environmental fungal antigens.
变应性气道疾病的特征是嗜酸性粒细胞炎症、黏液分泌过多和气道阻力增加。真菌抗原在环境中普遍存在，是众所周知的变应性疾病触发因素。细菌产物在环境中也经常遇到，可能会改变对某些抗原的免疫反应。同时暴露于细菌和真菌产物对肺部适应性免疫反应的影响尚未得到研究。在这里，我们表明经口咽吸入真菌裂解物（白色念珠菌、烟曲霉）可促进气道嗜酸性粒细胞增多、Th2细胞因子分泌和黏液细胞化生。相比之下，经口咽暴露于细菌裂解物（铜绿假单胞菌）会促进以中性粒细胞、Th1细胞因子分泌且无黏液产生为特征的气道炎症。更重要的是，将细菌裂解物与真菌裂解物一起给予会使适应性免疫反应偏向与嗜中性粒细胞增多和黏液产生减少相关的Th1型。细菌裂解物对真菌反应的免疫调节作用不依赖于Toll样受体4（TLR4），但依赖于髓样分化因子88（MyD88）。因此，气道内不同类型的微生物产物可改变宿主的适应性免疫反应，并可能影响对环境真菌抗原的变应性气道疾病的发展。
