Probing Immune-Mediated Clearance of Acute Middle Ear Infection in Mice.

Probing Immune-Mediated Clearance of Acute Middle Ear Infection in Mice.
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DOI:
10.3389/fcimb.2021.815627
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发表时间:
2021
影响因子:
5.7
通讯作者:
Harvill ET
Harvill ET
中科院分区:
医学2区
文献类型:
--
作者:
Dewan KK;Sedney C;Caulfield AD;Su Y;Ma L;Blas-Machado U;Harvill ET

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急性中耳炎 (AOM) 通常是由鼻咽部的细菌病原体引起,这些细菌沿着咽鼓管上升,导致中耳疾病。为了模拟和研究 AOM 的各种复杂性,将常见的人类耳病原体直接注射到啮齿类动物的中耳大疱中,或者与病毒共同感染一起递送,这有助于以复杂且部分理解的方式进入中耳。在这里,我们提出了新的观察结果,即支气管败血博德特氏菌(Bordetella bronchiseptica)是一种明确的小鼠呼吸道共生菌/病原体,也能有效地沿着咽鼓管上升到中耳,为研究自然发生的 AOM 提供了一个灵活的小鼠模型。缺乏 T 和/或 B 细胞的小鼠未能解决感染问题,这凸显了两者在清除中耳感染方面的合作作用。过继转移的抗体为肺部提供了完全保护,但仅部分保护了中耳,凸显了呼吸系统和耳免疫学之间的差异。我们将其作为一种新颖的实验系统提出,该系统可以利用小鼠模型的优势来剖析中耳内免疫生成和功能所涉及的分子机制。
Acute otitis media (AOM) is commonly caused by bacterial pathobionts of the nasopharynx that ascend the Eustachian tube to cause disease in the middle ears. To model and study the various complexities of AOM, common human otopathogens are injected directly into the middle ear bullae of rodents or are delivered with viral co-infections which contribute to the access to the middle ears in complex and partially understood ways. Here, we present the novel observation that Bordetella bronchiseptica, a well-characterized respiratory commensal/pathogen of mice, also efficiently ascends their Eustachian tubes to colonize their middle ears, providing a flexible mouse model to study naturally occurring AOM. Mice lacking T and/or B cells failed to resolve infections, highlighting the cooperative role of both in clearing middle ear infection. Adoptively transferred antibodies provided complete protection to the lungs but only partially protected the middle ears, highlighting the differences between respiratory and otoimmunology. We present this as a novel experimental system that can capitalize on the strengths of the mouse model to dissect the molecular mechanisms involved in the generation and function of immunity within the middle ear.
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