Inflammation Immunobiology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Lung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Viruses. 2020 Aug 27;12(9):946. doi: 10.3390/v12090946.
Chronic inhalation of fungi and fungal components has been linked to the development of respiratory disorders, although their role with respect to the pathogenesis of acute respiratory virus infection remains unclear. Here, we evaluate inflammatory pathology induced by repetitive administration of a filtrate of the ubiquitous fungus, , and its impact on susceptibility to infection with influenza A. We showed previously that at the nasal mucosae resulted in increased susceptibility to an otherwise sublethal inoculum of influenza A in wild-type mice. Here we demonstrate that -induced potentiation of influenza A infection was not dependent on fungal serine protease or ribonuclease activity. Repetitive challenge with prior to virus infection resulted proinflammatory cytokines, neutrophil recruitment, and loss of alveolar macrophages to a degree that substantially exceeded that observed in response to influenza A infection alone. Concomitant administration of immunomodulatory , a strategy shown previously to limit virus-induced inflammation in the airways, blocked the exaggerated lethal response. These observations promote an improved understanding of severe influenza infection with potential clinical relevance for individuals subjected to continuous exposure to molds and fungi.
慢性吸入真菌及其成分与呼吸道疾病的发展有关，尽管它们在急性呼吸道病毒感染发病机制中的作用尚不清楚。在这里，我们评估了重复给予无处不在的真菌的滤液引起的炎症病理学，及其对甲型流感感染易感性的影响。我们之前曾表明，在野生型小鼠的鼻黏膜中，导致对原本亚致死剂量的甲型流感感染的易感性增加。在这里，我们证明，-诱导的甲型流感感染增强不依赖于真菌丝氨酸蛋白酶或核糖核酸酶活性。在病毒感染之前用重复挑战导致促炎细胞因子、中性粒细胞募集和肺泡巨噬细胞的损失，其程度大大超过单独感染甲型流感时观察到的程度。同时给予免疫调节剂，这一策略先前已被证明可限制气道中病毒引起的炎症，可阻断过度的致命反应。这些观察结果促进了对严重流感感染的更好理解，对于持续暴露于霉菌和真菌的个体具有潜在的临床相关性。
