Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
Front Cell Infect Microbiol. 2023 Dec 6;13:1288057. doi: 10.3389/fcimb.2023.1288057. eCollection 2023.
The efficacy of the adaptive immune system in the middle ear (ME) is well established, but the mechanisms are not as well defined as those of gastrointestinal or respiratory tracts. While cellular elements of the adaptive response have been detected in the MEs following infections (or intranasal immunizations), their specific contributions to protecting the organ against reinfections are unknown. How immune protection mechanisms of the MEs compares with those in the adjacent and attached upper and lower respiratory airways remains unclear. To address these knowledge gaps, we used an established mouse respiratory infection model that we recently showed also involves ME infections. delivered to the external nares of mice in tiny numbers very efficiently infects the respiratory tract and ascends the Eustachian tube to colonize and infect the MEs, where it causes severe but acute inflammation resembling human acute otitis media (AOM). Since this AOM naturally resolves, we here examine the immunological mechanisms that clear infection and protect against subsequent infection, to guide efforts to induce protective immunity in the ME. Our results show that once the MEs are cleared of a primary infection, the convalescent organ is strongly protected from reinfection by the pathogen despite its persistence in the upper respiratory tract, suggesting important immunological differences in these adjacent and connected organs. CD4+ and CD8+ T cells trafficked to the MEs following infection and were necessary to robustly protect against secondary challenge. Intranasal vaccination with heat killed conferred robust protection against infection to the MEs, even though the nasopharynx itself was only partially protected. These data establish the MEs as discrete effector sites of adaptive immunity and shows that effective protection in the MEs and the respiratory tract is significantly different. This model system allows the dissection of immunological mechanisms that can prevent bacteria in the nasopharynx from ascending the ET to colonize the ME.
中耳（ME）的适应性免疫系统的功效已得到充分证实，但机制不如胃肠道或呼吸道那样明确。虽然在感染（或鼻内免疫接种）后已在 ME 中检测到适应性反应的细胞成分，但它们对保护器官免受再感染的具体贡献尚不清楚。ME 的免疫保护机制与相邻和附着的上呼吸道和下呼吸道的保护机制有何不同尚不清楚。为了解决这些知识空白，我们使用了一种已建立的小鼠呼吸道感染模型，我们最近的研究表明该模型还涉及 ME 感染。非常少量的 递送到小鼠的外鼻孔中，可非常有效地感染呼吸道，并通过咽鼓管上升，定植和感染 ME，从而引起类似于人类急性中耳炎（AOM）的严重但急性炎症。由于这种 AOM 自然消退，我们在此检查了清除感染并防止随后感染的免疫机制，以指导在 ME 中诱导保护性免疫的努力。我们的研究结果表明，一旦 ME 清除了原发性 感染，尽管病原体在上呼吸道中持续存在，但恢复期器官仍受到强烈保护，免受再次感染，这表明这些相邻和相连的器官之间存在重要的免疫差异。感染后，CD4+和 CD8+T 细胞迁移到 ME 中，对于强烈保护免受二次攻击是必需的。用加热杀死的 进行鼻内疫苗接种可对 ME 产生强大的抗感染保护作用，尽管鼻咽本身仅部分受到保护。这些数据确立了 ME 作为适应性免疫的离散效应部位，并表明 ME 和呼吸道中的有效保护明显不同。该模型系统允许对可以防止鼻咽中的细菌上升到 ET 定植 ME 的免疫机制进行剖析。
