Laboratory of Lung Biology, Department of Pathobiological Sciences and Center for Lung Biology and Disease, School of Veterinary Medicine, Louisiana State University (LSU) and Agricultural & Mechanical College, Baton Rouge, LA, United States.
Section of Pulmonary and Critical Care Department of Medicine, LSU Health Sciences Center, New Orleans, LA, United States.
Front Immunol. 2023 Aug 16;14:1249098. doi: 10.3389/fimmu.2023.1249098. eCollection 2023.
The respiratory system exposed to microorganisms continuously, and the pathogenicity of these microbes not only contingent on their virulence factors, but also the host's immunity. A multifaceted innate immune mechanism exists in the respiratory tract to cope with microbial infections and to decrease tissue damage. The key cell types of the innate immune response are macrophages, neutrophils, dendritic cells, epithelial cells, and endothelial cells. Both the myeloid and structural cells of the respiratory system sense invading microorganisms through binding or activation of pathogen-associated molecular patterns (PAMPs) to pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) and NOD-like receptors (NLRs). The recognition of microbes and subsequent activation of PRRs triggers a signaling cascade that leads to the activation of transcription factors, induction of cytokines/5chemokines, upregulation of cell adhesion molecules, recruitment of immune cells, and subsequent microbe clearance. Since numerous microbes resist antimicrobial agents and escape innate immune defenses, in the future, a comprehensive strategy consisting of newer vaccines and novel antimicrobials will be required to control microbial infections. This review summarizes key findings in the area of innate immune defense in response to acute microbial infections in the lung. Understanding the innate immune mechanisms is critical to design host-targeted immunotherapies to mitigate excessive inflammation while controlling microbial burden in tissues following lung infection.
呼吸系统不断接触微生物，这些微生物的致病性不仅取决于其毒力因子，还取决于宿主的免疫力。呼吸道存在多种先天免疫机制来应对微生物感染并减少组织损伤。先天免疫反应的关键细胞类型包括巨噬细胞、中性粒细胞、树突状细胞、上皮细胞和内皮细胞。呼吸系统的髓系和结构细胞通过结合或激活病原体相关分子模式（PAMPs）来识别入侵的微生物，从而识别模式识别受体（PRRs），包括 Toll 样受体（TLRs）和 NOD 样受体（NLRs）。微生物的识别和随后的 PRR 激活触发信号级联反应，导致转录因子的激活、细胞因子/趋化因子的诱导、细胞黏附分子的上调、免疫细胞的募集以及随后的微生物清除。由于许多微生物对抗生素有抵抗力并逃避先天免疫防御，因此，未来需要一种包含新型疫苗和新型抗菌药物的综合策略来控制微生物感染。本文综述了肺部急性微生物感染中先天免疫防御的关键发现。了解先天免疫机制对于设计针对宿主的免疫疗法至关重要，以减轻肺部感染后组织中过度炎症的同时控制微生物负荷。
