Department of Chemical and Biological Engineering, University of Colorado - Boulder, Boulder, CO, United States.
Front Immunol. 2021 Apr 27;12:661537. doi: 10.3389/fimmu.2021.661537. eCollection 2021.
Neutrophils are the primary responders to infection, rapidly migrating to sites of inflammation and clearing pathogens through a variety of antimicrobial functions. This response is controlled by a complex network of signals produced by vascular cells, tissue resident cells, other immune cells, and the pathogen itself. Despite significant efforts to understand how these signals are integrated into the neutrophil response, we still do not have a complete picture of the mechanisms regulating this process. This is in part due to the inherent disadvantages of the most-used experimental systems: systems lack the complexity of the tissue microenvironment and animal models do not accurately capture the human immune response. Advanced microfluidic devices incorporating relevant tissue architectures, cell-cell interactions, and live pathogen sources have been developed to overcome these challenges. In this review, we will discuss the models currently being used to study the neutrophil response to infection, specifically in the context of cell-cell interactions, and provide an overview of their findings. We will also provide recommendations for the future direction of the field and what important aspects of the infectious microenvironment are missing from the current models.
中性粒细胞是感染的主要反应细胞，它们通过多种抗菌功能迅速迁移到炎症部位并清除病原体。这种反应受到血管细胞、组织驻留细胞、其他免疫细胞和病原体本身产生的复杂信号网络的控制。尽管人们为了理解这些信号是如何整合到中性粒细胞反应中做出了巨大的努力，但我们仍然没有完全了解调节这一过程的机制。这在一定程度上是由于最常用的实验系统存在固有缺陷：这些系统缺乏组织微环境的复杂性，而动物模型并不能准确地捕捉到人类的免疫反应。已经开发出了结合相关组织架构、细胞-细胞相互作用和活病原体来源的先进微流控设备，以克服这些挑战。在这篇综述中，我们将讨论目前用于研究中性粒细胞对感染反应的模型，特别是在细胞-细胞相互作用方面，并概述它们的研究结果。我们还将为该领域的未来发展方向提供建议，并指出当前模型中缺少感染微环境的哪些重要方面。
