Loghmani A, Raoofi R, Ownagh A, Delirezh N
Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
Department of Infectious Diseases, University of Jahrom Medical Science, Jahrom, Iran.
Allergol Immunopathol (Madr). 2017 Mar-Apr;45(2):175-182. doi: 10.1016/j.aller.2016.07.005. Epub 2016 Nov 4.
Although the mechanism of asthma is not precisely understood in humans, clinical and epidemiological studies have offered a potential relationship between exposure to environmental fungi, such as Alternaria alternata (A. alternata) and the development and exacerbation of asthma. The aim of this project is to investigate the mechanisms of Th2 responses by A. alternata as a clinically relevant model for the environmental exposure.
Plastic adherent monocytes were cultured with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) to convert these cells into Monocyte-derived Dendritic cells (MoDc) and then matured in the presence of Monocyte-Conditioned Medium (MCM) as the control group and MCM+ A. alternata extract as the inductive groups.
The results indicated that the expression of CD14 decreased and CD83 and anti-human leukocyte antigen-DR (HLA-DR) increased in the inductive groups in comparison with the control group. More importantly, A. alternata inhibited IL-12 production by activated dendritic cells (DCs), and the DCs exposed to A. alternata enhanced the Th2 polarisation of CD4 T cells. The production amount of IL-10 overcame IL-12 as well as Il-23 increased significantly, and hand in T cells the production of cytokines Interferon-γ (IFN-γ) decreased. However, both IL-17 and IL-4 increased (p<0.05). Phagocytic activity in the inductive groups decreased significantly compared with the control group.
The asthma-related environmental fungus A. alternata, with an effect on dendritic cells profile mediates TH2/TH17. Such immunodysregulation properties of causative environmental fungi may explain their strong relationship with human asthma and allergic diseases.
尽管人类哮喘的发病机制尚未完全明确，但临床和流行病学研究表明，接触环境真菌（如链格孢菌）与哮喘的发生和加重之间可能存在潜在联系。本项目旨在研究链格孢菌引发Th2反应的机制，将其作为环境暴露的临床相关模型。
将塑料贴壁单核细胞与粒细胞巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-4（IL-4）共同培养，使其转化为单核细胞衍生树突状细胞（MoDc），然后在单核细胞条件培养基（MCM）作为对照组以及MCM +链格孢菌提取物作为诱导组的条件下使其成熟。
结果表明，与对照组相比，诱导组中CD14的表达降低，而CD83和抗人白细胞抗原-DR（HLA-DR）的表达增加。更重要的是，链格孢菌抑制活化树突状细胞（DC）产生IL-12，且暴露于链格孢菌的DC增强了CD4 T细胞的Th2极化。IL-10的产生量超过IL-12，同时IL-23显著增加，并且在T细胞中细胞因子干扰素-γ（IFN-γ）的产生减少。然而，IL-17和IL-4均增加（p<0.05）。与对照组相比，诱导组的吞噬活性显著降低。
与哮喘相关的环境真菌链格孢菌通过影响树突状细胞谱介导TH2/TH17。致病性环境真菌的这种免疫调节异常特性可能解释了它们与人类哮喘和过敏性疾病的密切关系。
