Alternaria alternata challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza virus infection.
Alternaria alternata challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza virus infection.
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DOI：
10.1111/cea.13123
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Rosenberg HF
中科院分区：
文献类型：
--
作者：
Ma M;Redes JL;Percopo CM;Druey KM;Rosenberg HF
鼻黏膜嗜酸性粒细胞是变应性鼻炎的基本特征。我们的目的是探讨嗜酸性粒细胞炎症及其对鼻黏膜呼吸道病毒感染的影响。在反复刺激小鼠鼻黏膜炎症的反应中，用严格的鼻内交替菌滤液量进行了评估。然后用流感病毒攻击小鼠。交替藤的重复刺激导致嗜酸性粒细胞向鼻道募集，与IL-5、IL-13和eotaxin-1水平升高有关；eotaxin-1−/−小鼠的嗜酸性粒细胞募集减少，Rag1−/−小鼠的嗜酸性粒细胞募集消失。在野生型和嗜酸性粒细胞缺乏ΔdblGATA小鼠中，交替a也导致鼻洗IgA水平升高。有趣的是，与单独接受稀释液治疗的小鼠相比，经A. alternta治疗的小鼠对流感病毒感染有明显的体重减轻和死亡率（0% vs 100%生存率，***p < 0.001）；当交替孢霉被热灭活后，致命反应减弱。检测到病毒滴度的微小差异，并且在病毒接种时鼻腔通道中存在的嗜酸性粒细胞对致命的后遗症没有保护作用。有趣的是，用交替假单胞菌处理过的小鼠的鼻洗液中含有更多的中性粒细胞和更高水平的促炎介质，以应对病毒的攻击，其中包括IL-6，一种人类流感疾病严重程度的生物标志物。反复给药可导致鼻黏膜炎症和意外的发病率和死亡率，以应对随后的流感病毒的挑战。有趣的是，与下呼吸道的研究结果相反，鼻道吸收的嗜酸性粒细胞对致命感染没有保护作用。由于鼻炎患者对流感病毒的易感性增加已成为一些临床报告的主题，因此该模型可用于进一步探索这些观察结果。
Eosinophils in the nasal mucosa are an elemental feature of allergic rhinitis. Our objective was to explore eosinophilic inflammation and its impact on respiratory virus infection at the nasal mucosa. Inflammation in the nasal mucosae of mice was evaluated in response to repetitive stimulation with strict intranasal volumes of a filtrate of Alternaria alternata. Mice were then challenged with influenza virus. Repetitive stimulation with A. alternata resulted in eosinophil recruitment to the nasal passages in association with elevated levels of IL-5, IL-13, and eotaxin-1; eosinophil recruitment was diminished in eotaxin-1−/− mice, and abolished in Rag1−/− mice. A. alternata also resulted in elevated levels of nasal-wash IgA in both wild-type and eosinophil-deficient ΔdblGATA mice. Interestingly, A. alternata-treated mice responded to an influenza virus infection with profound weight loss and mortality compared to mice that received diluent alone (0% vs. 100% survival, ***p < 0.001); the lethal response was blunted when A. alternata was heat-inactivated. Minimal differences in virus titer were detected, and eosinophils present in the nasal passages at the time of virus inoculation provided no protection against the lethal sequelae. Interestingly, nasal-wash fluids from mice treated with A. alternata included more neutrophils and higher levels of proinflammatory mediators in response to virus challenge, among these, IL-6, a biomarker for disease severity in human influenza. Repetitive administration of A. alternata resulted in inflammation of the nasal mucosae and unanticipated morbidity and mortality in response to subsequent challenge with influenza virus. Interestingly, and in contrast to findings in the lower airways, eosinophils recruited to the nasal passages provided no protection against lethal infection. As increased susceptibility to influenza virus among individuals with rhinitis has been the subject of several clinical reports, this model may be used for further exploration of these observations.
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