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反复暴露后,持续存在的酵母物种会引起小鼠独特的气道炎症。

Persisting yeast species and elicit unique airway inflammation in mice following repeated exposure.

机构信息

Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV, United States.

Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, United States.

出版信息

Front Cell Infect Microbiol. 2023 Feb 14;13:1067475. doi: 10.3389/fcimb.2023.1067475. eCollection 2023.

Abstract

BACKGROUND

Allergic airway disease (AAD) is a growing concern in industrialized nations and can be influenced by fungal exposures. Basidiomycota yeast species such as are known to exacerbate allergic airway disease; however, recent indoor assessments have identified other Basidiomycota yeasts, including (syn. ), to be prevalent and potentially associated with asthma. Until now, the murine pulmonary immune response to repeated exposure was previously unexplored.

OBJECTIVE

This study aimed to compare the immunological impact of repeated pulmonary exposure to yeasts.

METHODS

Mice were repeatedly exposed to an immunogenic dose of or oropharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and lungs were collected to examine airway remodeling, inflammation, mucous production, cellular influx, and cytokine responses at 1 day and 21 days post final exposure. The responses to and were analyzed and compared.

RESULTS

Following repeated exposure, both and cells were still detectable in the lungs 21 days post final exposure. Repeated exposure initiated myeloid and lymphoid cellular infiltration into the lung that worsened over time, as well as an IL-4 and IL-5 response compared to PBS-exposed controls. In contrast, repeated exposure induced a strong CD4 T cell-driven lymphoid response that started to resolve by 21 days post final exposure.

DISCUSSION

remained in the lungs and exacerbated the pulmonary immune responses as expected following repeated exposure. The persistence of in the lung and strong lymphoid response following repeated exposure were unexpected given its lack of reported involvement in AAD. Given the abundance in indoor environments and industrial utilization of , these results highlight the importance to investigate the impact of frequently detected fungal organisms on the pulmonary response following inhalational exposure. Moreover, it is important to continue to address the knowledge gap involving Basidiomycota yeasts and their impact on AAD.

摘要

背景

变应性气道疾病(AAD)在工业化国家日益受到关注,并且可能受到真菌暴露的影响。众所周知,担子菌酵母物种如会加剧变应性气道疾病;然而,最近的室内评估已经确定了其他担子菌酵母,包括(syn. ),普遍存在并可能与哮喘有关。到目前为止,反复暴露于对肺部的免疫反应尚未被探索。

目的

本研究旨在比较反复肺部暴露于 酵母的免疫影响。

方法

通过口咽吸入,将小鼠反复暴露于免疫原性剂量的或。收集支气管肺泡灌洗液(BALF)和肺,以在最后一次暴露后 1 天和 21 天检查气道重塑、炎症、粘液产生、细胞浸润和细胞因子反应。分析并比较了对和的反应。

结果

在最后一次暴露后 21 天,肺中仍可检测到和细胞。反复暴露会引发骨髓和淋巴样细胞向肺部浸润,随着时间的推移会加重,并引发与 PBS 暴露对照相比的 IL-4 和 IL-5 反应。相比之下,反复暴露会引发强烈的 CD4 T 细胞驱动的淋巴样反应,该反应在最后一次暴露后 21 天开始缓解。

讨论

与预期的一样,在反复暴露后,仍存在于肺部,并加剧了肺部免疫反应。与缺乏报道的变应性气道疾病参与情况相反,在肺部中持续存在和反复暴露后引发强烈的淋巴样反应是出乎意料的。鉴于其在室内环境中的丰富度和工业利用,这些结果强调了研究频繁检测到的真菌对吸入暴露后肺部反应的重要性。此外,继续解决涉及担子菌酵母及其对 AAD 影响的知识差距也很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12c4/9971225/9dbe61008cc3/fcimb-13-1067475-g001.jpg

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