Human Health Therapeutics Research Center, National Research Council Canada, Ottawa, Ontario, Canada.
Chelation Partners Inc., Halifax, Nova Scotia, Canada.
Infect Immun. 2019 Oct 18;87(11). doi: 10.1128/IAI.00591-19. Print 2019 Nov.
Porcine mucin has been commonly used to enhance the infectivity of bacterial pathogens, including , in animal models, but the mechanisms for enhancement by mucin remain relatively unknown. In this study, using the mouse model of intraperitoneal (i.p.) mucin-enhanced infection, we characterized the kinetics of bacterial replication and dissemination and the host innate immune responses, as well as their potential contribution to mucin-enhanced bacterial virulence. We found that mucin, either admixed with or separately injected with the challenge bacterial inoculum, was able to enhance the tissue and blood burdens of strains of different virulence. Intraperitoneal injection of -mucin or mucin alone induced a significant but comparable reduction of peritoneal macrophages and lymphocytes, accompanied by a significant neutrophil recruitment and early interleukin-10 (IL-10) responses, suggesting that the resulting inflammatory cellular and cytokine responses were largely induced by the mucin. Depletion of peritoneal macrophages or neutralization of endogenous IL-10 activities showed no effect on the mucin-enhanced infectivity. However, pretreatment of mucin with iron chelator DIBI, but not deferoxamine, partially abolished its virulence enhancement ability, and replacement of mucin with iron significantly enhanced the bacterial burdens in the peritoneal cavity and lung. Taken together, our results favor the hypothesis that iron at least partially contributes to the mucin-enhanced infectivity of in this model.
猪黏蛋白常用于增强细菌病原体的感染力，包括在动物模型中，但黏蛋白增强的机制仍相对未知。在这项研究中，我们使用腹腔内（i.p.）黏蛋白增强感染的小鼠模型，描述了细菌复制和传播的动力学以及宿主先天免疫反应，以及它们对黏蛋白增强细菌毒力的潜在贡献。我们发现，无论是与挑战细菌接种物混合还是单独注射的黏蛋白，都能够增强不同毒力的 菌株的组织和血液负担。腹腔内注射 -黏蛋白或单独注射黏蛋白会引起明显但相当的腹腔巨噬细胞和淋巴细胞减少，同时伴有明显的中性粒细胞募集和早期白细胞介素-10（IL-10）反应，表明由此产生的炎症细胞和细胞因子反应主要是由黏蛋白诱导的。腹腔巨噬细胞耗竭或内源性 IL-10 活性的中和对黏蛋白增强的感染性没有影响。然而，用铁螯合剂 DIBI 预处理黏蛋白，但不是去铁胺，部分消除了其增强毒力的能力，并用铁替代黏蛋白显著增加了腹腔和肺部的细菌负担。总之，我们的结果支持这样一种假设，即铁至少部分参与了该模型中 黏蛋白增强的感染性。
