Hymøller Kirstine Mejlstrup, Christiansen Stig Hill, Schlosser Anders Grønnegaard, Skov Sørensen Uffe B, Lee Jean C, Thiel Steffen
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
The Centre for Cellular Signal Patterns (CellPAT), Aarhus University, Aarhus, Denmark.
Front Immunol. 2025 Jan 7;15:1504886. doi: 10.3389/fimmu.2024.1504886. eCollection 2024.
The innate immune system plays a critical role in the rapid recognition and elimination of pathogens through pattern recognition receptors (PRRs). Among these PRRs are the C-type lectins (CTLs) langerin, mannan-binding lectin (MBL), and surfactant protein D (SP-D), which recognize carbohydrate patterns on pathogens. Each represents proteins from different compartments of the body and employs separate effector mechanisms. We have investigated their interaction with the Gram-positive opportunistic pathogen , a bacterium whose cell wall contains two key glycopolymers: capsular polysaccharide (CP) and wall teichoic acid (WTA). Using a langerin-expressing cell line and recombinant langerin, MBL, and SP-D, we demonstrated that langerin, MBL, and SP-D all recognize nonencapsulated S. However, the bacterium may produce CP that effectively shields from recognition by all three CTLs. Experiments utilizing mutant strains confirmed that WTA is a ligand for MBL, but that langerin likely interacts with an additional unknown ligand. A competition assay revealed that MBL and SP-D inhibit langerin's interaction with , highlighting the intricate redundancy and cooperation within the innate immune system. This study highlights the dynamic interplay of langerin, MBL, and SP-D in recognizing specific surface structures on and provides insight into how this pathogen evades innate immune recognition.
固有免疫系统通过模式识别受体(PRR)在病原体的快速识别和清除中发挥关键作用。这些PRR包括C型凝集素(CTL)、朗格汉斯蛋白(langerin)、甘露糖结合凝集素(MBL)和表面活性蛋白D(SP-D),它们识别病原体上的碳水化合物模式。每种蛋白都代表来自身体不同部位的蛋白质,并采用不同的效应机制。我们研究了它们与革兰氏阳性机会致病菌的相互作用,该细菌的细胞壁含有两种关键糖聚合物:荚膜多糖(CP)和壁磷壁酸(WTA)。使用表达朗格汉斯蛋白的细胞系以及重组朗格汉斯蛋白、MBL和SP-D,我们证明朗格汉斯蛋白、MBL和SP-D都能识别无荚膜的该种细菌。然而,该细菌可能产生CP,有效地屏蔽了这三种CTL的识别。利用突变菌株进行的实验证实,WTA是MBL的配体,但朗格汉斯蛋白可能与另一种未知配体相互作用。竞争试验表明,MBL和SP-D抑制朗格汉斯蛋白与该种细菌的相互作用,突出了固有免疫系统内复杂的冗余和协作。这项研究突出了朗格汉斯蛋白、MBL和SP-D在识别该种细菌特定表面结构方面的动态相互作用,并深入了解了这种病原体如何逃避固有免疫识别。