Lysozyme is a β-1,4-glycosidase that hydrolyzes the polysaccharide backbone of bacterial cell walls. With an additional bactericidal function mediated by a separate protein domain, lysozyme is considered a uniquely important antimicrobial molecule contributing to the host's innate immune response to infection. Elevated lysozyme production is found in various inflammatory conditions while patients with genetic risks for inflammatory bowel diseases demonstrate abnormal lysozyme expression, granule packaging, and secretion in Paneth cells. However, it remains unclear how a gain- or loss-of-function in host lysozyme may impact the host inflammatory responses to pathogenic infection. We challenged and ectopic -expressing () mice with . and then comprehensively assessed the inflammatory disease progression. We conducted proteomics analysis to identify molecules derived from human lysozyme-mediated processing of live . We examined the barrier-impairing effects of these identified molecules in human intestinal epithelial cell monolayer and enteroids. mice are protected from infection in terms of morbidity, mortality, and barrier integrity, whereas mice demonstrate exacerbated infection and inflammation. The growth and invasion of are not affected by human or chicken lysozyme, whereas lysozyme encountering of live stimulates the release of barrier-disrupting factors, InvE-sipC and Lpp1, which directly or indirectly impair the tight junctions. The direct engagement of host intestinal lysozyme with an enteric pathogen such as promotes the release of virulence factors that are barrier-impairing and pro-inflammatory. Controlling lysozyme function may help alleviate the inflammatory progression.

中文翻译：

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鼠伤寒沙门氏菌的肠道溶菌酶参与刺激屏障受损 InvE 和 Lpp1 的释放


溶菌酶是一种 β-1,4-糖苷酶，可水解细菌细胞壁的多糖骨架。溶菌酶具有由单独的蛋白质结构域介导的额外杀菌功能，被认为是一种独特重要的抗菌分子，有助于宿主对感染的先天免疫反应。在各种炎症条件下都发现溶菌酶产生升高，而具有炎症性肠病遗传风险的患者在潘氏细胞中表现出溶菌酶表达、颗粒包装和分泌异常。然而，目前尚不清楚宿主溶菌酶功能的获得或丧失如何影响宿主对病原体感染的炎症反应。我们用 . 攻击异位表达 () 小鼠。然后综合评估炎症性疾病的进展情况。我们进行了蛋白质组学分析，以鉴定源自人类溶菌酶介导的活体加工的分子。我们检查了这些已识别分子在人肠上皮细胞单层和肠样细胞中的屏障损害作用。小鼠在发病率、死亡率和屏障完整性方面免受感染，而小鼠则表现出严重的感染和炎症。活菌的生长和侵袭不受人或鸡溶菌酶的影响，而活菌遇到溶菌酶会刺激屏障破坏因子InvE-sipC和Lpp1的释放，直接或间接损害紧密连接。宿主肠道溶菌酶与肠道病原体的直接接触，例如促进损伤屏障和促炎的毒力因子的释放。控制溶菌酶功能可能有助于减轻炎症进展。