Toll样受体2在小鼠慢性真菌性哮喘期间调节先天性和适应性免疫反应。

Toll like receptor-2 modulates both innate and adaptive immune responses during chronic fungal asthma in mice.

作者信息

Buckland K F, O'Connor E, Murray L A, Hogaboam C M

机构信息

Immunology Program, Department of Pathology, University of Michigan Medical School, Rm 4057, BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.

出版信息

Inflamm Res. 2008 Aug;57(8):379-87. doi: 10.1007/s00011-008-8004-y.

DOI:10.1007/s00011-008-8004-y

PMID:18787777

Abstract

OBJECTIVE AND DESIGN

We investigated the effect of TLR2 gene deletion in a murine model of chronic fungal asthma.

METHODS

TLR2 wildtype (TLR2(+/+)) and TLR2 deficient (TLR2(-/-)) mice were sensitized to soluble A. fumigatus antigens and challenged with live A. fumigatus conidia, and the extent of allergic airways disease was analyzed in both groups of mice at 3, 7, 14, and 30 days after conidia.

RESULTS

At day 7 post-conidia, TLR2(-/-) mice exhibited significantly lower airway hyperresponsiveness, airway inflammation, and whole lung Th2 cytokine levels compared with the TLR2(+ / +) group. TLR2 deletion also significantly reduced mucus cell metaplasia and peribronchial fibrosis at day 30 after conidia. However, fungal material persisted in the TLR2(-/-) group, and at day 30 after conidia TLR2(-/-) mice exhibited enhanced airway neutrophil recruitment and airway hyperresponsiveness.

CONCLUSION

Thus, during chronic fungal asthma in mice, TLR2 is a major contributor to the maintenance of the adaptive Th2-cytokine driven and anti-fungal innate responses.

摘要

目的与设计

我们在慢性真菌性哮喘小鼠模型中研究了TLR2基因缺失的影响。

方法

将TLR2野生型（TLR2(+/+)）和TLR2缺陷型（TLR2(-/-)）小鼠用烟曲霉可溶性抗原致敏，并用活的烟曲霉分生孢子攻击，在分生孢子攻击后3、7、14和30天分析两组小鼠的过敏性气道疾病程度。

结果

在分生孢子攻击后第7天，与TLR2(+/+)组相比，TLR2(-/-)小鼠表现出显著更低的气道高反应性、气道炎症和全肺Th2细胞因子水平。TLR2缺失在分生孢子攻击后第30天也显著减少了黏液细胞化生和支气管周围纤维化。然而，真菌物质在TLR2(-/-)组中持续存在，并且在分生孢子攻击后第30天，TLR2(-/-)小鼠表现出增强的气道中性粒细胞募集和气道高反应性。