Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
J Allergy Clin Immunol. 2013 Jul;132(1):159-69. doi: 10.1016/j.jaci.2013.01.003. Epub 2013 Feb 10.
It is well accepted that mold exposure is a major contributor to the development of asthma, and beta-glucans are often used as a surrogate for mold exposure in the environment. Beta-glucans are an important component of mold spores and are recognized by the immune system by their receptor, Dectin-1. Cladosporium cladosporioides spores have a high beta-glucan content, but the beta-glucans are not available on the surface of live spores.
We sought to determine whether altering the exposure of beta-glucans in C cladosporioides through heat killing could alter the immune response through binding to Dectin-1.
In a murine model of mold-induced asthma, mice were repeatedly exposed to either live or heat-killed C cladosporioides and the phenotype was determined by the measurement of airway hyperresponsiveness, airway inflammation, and cytokine production. Pro-inflammatory cytokines from dendritic cells were measured by using quantitative PCR and ELISA.
Live C cladosporioides induced robust airway hyperresponsiveness, eosinophilia, and a predominately TH2 response, while heat-killed C cladosporioides induced a strong TH17 response and neutrophilic inflammation, but very mild airway hyperresponsiveness. Heat killing of C cladosporioides spores effectively exposed beta-glucans on the surface of the spores and increased binding to Dectin-1. In the absence of Dectin-1, heat-killed spores induced a predominantly TH2 response analogous to live spores. Furthermore, the production of TH17-skewing IL-6, IL-23, and TNF-α by dendritic cells in response to heat-killed C cladosporioides was dependent on Dectin-1.
The host immune response to C cladosporioides is dependent on the surface availability of beta-glucans rather than the total beta-glucan content.
众所周知，霉菌暴露是哮喘发展的主要原因，β-葡聚糖通常用作环境中霉菌暴露的替代物。β-葡聚糖是霉菌孢子的重要组成部分，其受体 Dectin-1 可识别免疫系统。枝孢菌孢子的β-葡聚糖含量很高，但活孢子表面没有可用的β-葡聚糖。
我们试图确定通过热杀灭改变枝孢菌中β-葡聚糖的暴露是否可以通过与 Dectin-1 结合来改变免疫反应。
在霉菌诱导的哮喘的小鼠模型中，反复暴露于活的或热杀灭的 C cladosporioides，通过气道高反应性、气道炎症和细胞因子产生来确定表型。通过定量 PCR 和 ELISA 测量树突状细胞中的促炎细胞因子。
活的 C cladosporioides 诱导强烈的气道高反应性、嗜酸性粒细胞增多和主要的 TH2 反应，而热杀灭的 C cladosporioides 诱导强烈的 TH17 反应和中性粒细胞炎症，但气道高反应性非常轻微。枝孢菌孢子的热杀灭有效地暴露了孢子表面的β-葡聚糖，并增加了与 Dectin-1 的结合。在没有 Dectin-1 的情况下，热杀灭的孢子诱导类似于活孢子的主要 TH2 反应。此外，树突状细胞对热杀灭的 C cladosporioides 的反应中产生的偏向 TH17 的 IL-6、IL-23 和 TNF-α的产生依赖于 Dectin-1。
宿主对 C cladosporioides 的免疫反应取决于β-葡聚糖表面的可用性，而不是总β-葡聚糖含量。
