Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Nat Rev Immunol. 2019 May;19(5):291-304. doi: 10.1038/s41577-019-0124-9.
It is generally regarded that the progression of an infection within host macrophages is the consequence of a failed immune response. However, recent appreciation of macrophage heterogeneity, with respect to both development and metabolism, indicates that the reality is more complex. Different lineages of tissue-resident macrophages respond divergently to microbial, environmental and immunological stimuli. The emerging picture that the developmental origin of macrophages determines their responses to immune stimulation and to infection stresses the importance of in vivo infection models. Recent investigations into the metabolism of infecting microorganisms and host macrophages indicate that their metabolic interface can be a major determinant of pathogen growth or containment. This Review focuses on the integration of data from existing studies, the identification of challenges in generating and interpreting data from ongoing studies and a discussion of the technologies and tools that are required to best address future questions in the field.
一般认为，宿主巨噬细胞内感染的进展是免疫反应失败的结果。然而，最近对巨噬细胞异质性的认识，无论是在发育还是代谢方面，都表明现实更为复杂。不同谱系的组织驻留巨噬细胞对微生物、环境和免疫刺激的反应不同。新兴的观点认为，巨噬细胞的发育起源决定了它们对免疫刺激和感染的反应，这强调了体内感染模型的重要性。最近对感染微生物和宿主巨噬细胞代谢的研究表明，它们的代谢界面可能是病原体生长或控制的主要决定因素。这篇综述重点介绍了整合现有研究数据，确定正在进行的研究中产生和解释数据的挑战，并讨论了为该领域未来的问题提供最佳解决方案所需的技术和工具。
