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经鼻 CpG 疗法以 TLR9 依赖和非依赖的方式减轻实验性真菌性哮喘。

Intranasal CpG therapy attenuated experimental fungal asthma in a TLR9-dependent and -independent manner.

机构信息

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.

出版信息

Int Arch Allergy Immunol. 2010;152(2):98-112. doi: 10.1159/000265531. Epub 2009 Dec 16.

DOI:10.1159/000265531
PMID:20016192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2883833/
Abstract

BACKGROUND

CpG administration abolishes airway inflammation and remodeling in acute models of allergic airway disease.

METHODS

Herein, we investigated the therapeutic effect of CpG in a chronic fungal model of asthma. TLR9+/+ and TLR9-/- mice were sensitized to soluble Aspergillus fumigatus antigens and challenged with live A. fumigatus conidia. Mice were treated with intraperitoneal (IP) or intranasal (IN) CpG, or left untreated 14-28 days after conidium challenge. All features of allergic airway disease were attenuated in TLR9+/+ mice treated with IN CpG, including airway hyperresponsiveness (AHR), mucus production, and peribronchial fibrosis.

RESULTS

TLR9-/- mice treated with IN CpG exhibited attenuated airway remodeling but not AHR. Whole-lung IL-12 levels were significantly elevated in both TLR9+/+ and TLR9-/- mice receiving IN CpG but not in either group receiving IP CpG. Whole-lung IL-10 levels were significantly elevated in IN CpG-treated TLR9+/+ mice but not in TLR9-/- mice receiving IN CpG. Increased whole-lung transcript and protein levels of the scavenger receptors SR-A and MARCO were observed in TLR9-/- mice compared with TLR9+/+ mice, possibly accounting for the CpG responsiveness in the knockout group.

CONCLUSIONS

Together, these data show that IN CpG has a therapeutic effect during established fungal asthma, which is TLR9 dependent and independent.

摘要

背景

CpG 给药可消除变应性气道疾病急性模型中的气道炎症和重塑。

方法

在此，我们研究了 CpG 在慢性真菌性哮喘模型中的治疗作用。TLR9+/+和 TLR9-/-小鼠用可溶性烟曲霉抗原致敏，并接受活烟曲霉分生孢子攻击。在分生孢子攻击后 14-28 天，用腹腔内（IP）或鼻内（IN）CpG 治疗或不治疗小鼠。TLR9+/+小鼠用 IN CpG 治疗可减轻所有变应性气道疾病特征，包括气道高反应性（AHR）、黏液产生和支气管周围纤维化。

结果

用 IN CpG 治疗的 TLR9-/-小鼠表现出气道重塑减弱，但 AHR 未减弱。TLR9+/+和 TLR9-/-小鼠接受 IN CpG 治疗后，整个肺的 IL-12 水平显著升高，但接受 IP CpG 治疗的两组均未升高。IN CpG 治疗的 TLR9+/+小鼠的整个肺 IL-10 水平显著升高，但 TLR9-/-小鼠接受 IN CpG 治疗则不然。与 TLR9+/+小鼠相比，TLR9-/-小鼠的整个肺转录和蛋白水平的清道夫受体 SR-A 和 MARCO 均升高，这可能解释了敲除组对 CpG 的反应性。

结论

总之，这些数据表明，IN CpG 在已建立的真菌性哮喘中具有治疗作用，这种作用依赖于 TLR9，也不依赖于 TLR9。

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Toll-like receptor 9 modulates immune responses to Aspergillus fumigatus conidia in immunodeficient and allergic mice.Toll样受体9调节免疫缺陷和过敏小鼠对烟曲霉分生孢子的免疫反应。
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Immunomodulatory effects of CpG oligodeoxynucleotides on house dust mite-induced airway inflammation in mice.CpG寡脱氧核苷酸对屋尘螨诱导的小鼠气道炎症的免疫调节作用。
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