呼吸道病毒与气道上皮细胞的免疫调控

Immunoregulation by airway epithelial cells (AECs) against respiratory virus infection

气道是人体与外界交流的重要通道,每天人体经气道吸入空气可达10 000~20 000升,因此不可避免地需要与环境中大量的致病微生物长期接触。与"职业型(professional)"免疫细胞类似,气道上皮细胞(AECs)具有天然免疫功能,能侦测病原体(如不同种属的呼吸道病毒)的入侵并迅速产生宿主免疫反应。近年来的研究发现,为避免慢性炎症和维持免疫稳态,作为"非职业型(non-professional)"免疫细胞的AECs具有重要的调控气道局部免疫力的功能,这些功能包括:(1)AECs可高水平表达模式识别受体(PRRs),又称病原相关模式(PAMP),如Toll样受体家族(TLRs)、维A酸诱导基因Ⅰ(RIG-Ⅰ)样受体等,这些受体的存在使得AECs具有灵敏的病原侦测功能。(2)AECs通过调节天然免疫反应的灵敏度,发挥天然免疫和获得性免疫的调节器作用,在气道微环境中通过与"职业型"免疫细胞的互相作用,使针对病原体的宿主免疫反应达到可控的程度。(3)AECs免疫调节功能的缺失或破坏可能引起慢性气道炎症性疾病的发生和发展。本综述聚焦AECs如何通过直接作用和间接作用调控气道免疫能力,应对呼吸道病毒这一类重要的气道病原体感染,并着重阐明由于AECs调控机制的缺失和改变导致气道黏膜免疫功能失调和炎症(如急性和慢性鼻-鼻窦炎)的机制。

The respiratory tract is primary contact site of the body and environment, and it is ventilated by 10-20 thousand liters of air per day. Inevitably, the respiratory system comes into contact with airborne microbes, which contain the disease-causing pathogens. Airway epithelial cells（AECs） are known to have innate sensor functions, which are similar to the ＂professional＂ immune cells, such as alveolar macrophage and sub-or intra-epithelial dendritic cells（DCs）. Thus AECs are able to detect invading microbial danger including different types of respiratory viruses, and mount a potent host response, for example, activating type Ⅰ interferon signaling pathway genes. To avoid chronic inflammation and maintain the immunological homeostasis, the pulmonary system has developed intrinsic mechanisms to control local immune responses. Most recently, the role of AECs in control of local immunity has gained much attention, as 1） AECs express the pattern recognition receptors（PRRs）, such as Toll-like receptors, retinoic acid inducible gene Ⅰ（RIG-I）-like receptor, and so on, thus AECs are equipped to participate in innate detection of microbial encounter; 2） To keep immunological homeostasis in the respiratory tract, AECs behave not only as innate immune sensors but also as immune modulators in parallel, through modulating the sensitivity of innate immune sensing of both AECs per se and sub-or intra-epithelial immune cells; 3） Loss of modularity capacity of AECs might be involved in the development of chronic airway diseases. In present review, how the AECs act will be intensively discussed in response to respiratory viruses and modulate the local immunity through cis-and trans-factors（direct and indirect factors）, as well as the consequence of impairment of this control of local immunity, in the development and exacerbation of airway diseases, such as acute and chronic rhinosinusitis.