Halstead E Scott, Chroneos Zissis C
a 1 Department of Pediatrics, Division of Pulmonary Critical Care, Medicine, Pulmonary Immunology and Physiology Laboratory, Pennsylvania State University College of Medicine, Pennsylvania State University Hershey Children's Hospital, Hershey, PA, USA.
b 2 Department of Pediatrics, Microbiology and Immunology, Pulmonary Immunology and Physiology Laboratory, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Expert Rev Anti Infect Ther. 2015;13(12):1425-8. doi: 10.1586/14787210.2015.1094375. Epub 2015 Sep 28.
Alveolar macrophages (AMs) are critical for immunity against influenza A virus (IAV) infection. Depletion, hyporeactivity, and disruption of AM development and differentiation are all associated with lethal IAV infection. AMs drive the innate immune response that limits IAV infection. AMs are crucial for steady-state homeostasis of pulmonary surfactant, and in turn surfactant proteins regulate AMs and participate in host defense against IAV. Known factors that are necessary for AM function and differentiation in vivo include surfactant proteins, the growth factor GM-CSF, the hormone receptor PPARγ, and the transcription factors PU.1 and Bach2. Although PU.1 and PPARγ are downstream effectors of GM-CSF, Bach2 works independently. GM-CSF and Bach2-deficient AMs have phenotypes with immature or alternatively activated states of differentiation, respectively, and both extremes are unsuitable for surfactant homeostasis. The activation state of AMs and the local microenvironment may determine the development of symptomatic versus asymptomatic IAV infection in different individuals.
肺泡巨噬细胞（AMs）对于抵抗甲型流感病毒（IAV）感染的免疫反应至关重要。AMs的耗竭、反应性降低以及AMs发育和分化的破坏均与致死性IAV感染相关。AMs驱动限制IAV感染的固有免疫反应。AMs对于肺表面活性剂的稳态至关重要，而表面活性剂蛋白反过来调节AMs并参与宿主对IAV的防御。已知体内AMs功能和分化所必需的因素包括表面活性剂蛋白、生长因子GM-CSF、激素受体PPARγ以及转录因子PU.1和Bach2。尽管PU.1和PPARγ是GM-CSF的下游效应器，但Bach2独立发挥作用。GM-CSF缺陷型和Bach2缺陷型AMs分别具有分化不成熟或替代性激活状态的表型，而这两种极端情况均不适用于表面活性剂稳态。AMs的激活状态和局部微环境可能决定不同个体中症状性与无症状性IAV感染的发展。
