Glass Erin, Robinson Stephan L, Rosowski Emily E
Department of Biological Sciences, Clemson University, Clemson, SC.
Eukaryotic Pathogens Innovation Center, Clemson University, Clemson, SC.
bioRxiv. 2024 Jun 27:2024.06.24.600417. doi: 10.1101/2024.06.24.600417.
Pattern recognition receptors (PRRs) such as C-type lectin receptors (CLRs) and Toll-like receptors (TLRs) are used by hosts to recognize pathogen-associated molecular patterns (PAMPs) in microorganisms and to initiate innate immune responses. While PRRs exist across invertebrate and vertebrate species, the functional homology of many of these receptors is still unclear. In this study, we investigate the innate immune response of zebrafish larvae to zymosan, a β-glucan-containing particle derived from fungal cell walls. Macrophages and neutrophils robustly respond to zymosan and are required for zymosan-induced activation of the NF-κB transcription factor. Full activation of NF-κB in response to zymosan depends on Card9/Syk and Myd88, conserved CLR and TLR adaptor proteins, respectively. Two putative CLRs, Clec4c and Sclra, are both required for maximal sensing of zymosan and NF-κB activation. Altogether, we identify conserved PRRs and PRR signaling pathways in larval zebrafish that promote recognition of fungal PAMPs. These results inform modeling of human fungal infections in zebrafish and increase our knowledge of the evolution and conservation of PRR pathways in vertebrates.
模式识别受体（PRR），如C型凝集素受体（CLR）和Toll样受体（TLR），被宿主用来识别微生物中的病原体相关分子模式（PAMP）并启动先天免疫反应。虽然PRR存在于无脊椎动物和脊椎动物物种中，但许多这些受体的功能同源性仍不清楚。在本研究中，我们研究了斑马鱼幼体对酵母聚糖（一种源自真菌细胞壁的含β-葡聚糖颗粒）的先天免疫反应。巨噬细胞和中性粒细胞对酵母聚糖有强烈反应，并且是酵母聚糖诱导的NF-κB转录因子激活所必需的。响应酵母聚糖时NF-κB的完全激活分别取决于Card9/Syk和Myd88，它们分别是保守的CLR和TLR衔接蛋白。两个假定的CLR，Clec4c和Sclra，都是最大程度感知酵母聚糖和NF-κB激活所必需的。总之，我们在斑马鱼幼体中鉴定出促进真菌PAMP识别的保守PRR和PRR信号通路。这些结果为斑马鱼中人类真菌感染的建模提供了信息，并增加了我们对脊椎动物中PRR途径的进化和保守性的了解。
