J Allergy Clin Immunol:揭示IFN-λ1有利于正常鼻组织非鼻息肉情况下金黄色葡萄球菌清除

2019-04-26 不详 北京同仁医院

近日,首都医科大学附属北京同仁医院张罗教授团队在《Journal of Allergy and Clinical Immunology》发表题为“IFN-λ1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps”的论文。研究团队发现,正常鼻组织中IFN-λ1可通过IL-28

近日,首都医科大学附属北京同仁医院张罗教授团队在《Journal of Allergy and Clinical Immunology》发表题为“IFN-λ1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps”的论文。研究团队发现,正常鼻组织中IFN-λ1可通过IL-28R–JAK–STAT1-ROS信号通路增强巨噬细胞的功能,有利于金黄色葡萄球菌的清除;鼻息肉组织由于其自身巨噬细胞功能存在缺陷,IFN-λ1无法发挥其清除细菌的作用。

慢性鼻窦炎伴鼻息肉(CRSwNP)患者症状重,有些病患因疾病复发反复手术几十次,严重影响生活质量。课题组前期工作发现,CRSwNP患者鼻组织携带金黄色葡萄球菌明显高于正常人,且金黄色葡萄球菌数量与CRSwNP的严重程度和复发密切相关,主要原因是鼻息肉组织内2型巨噬细胞增多,其杀伤金黄色葡萄球菌的能力明显下降,持续存在的金黄色葡萄球菌导致炎症持续发酵。此外,呼吸道病毒与金黄色葡萄球菌存在协同作用,病毒的侵袭进一步加重炎症反应。然而,目前尚缺乏有效手段同时清除鼻粘膜中的病毒和细菌。临床上,干扰素已被用于抑制病毒复制,但其是否能够同时清除病毒和细菌,尚未可知。IFN-λ1是III型干扰素家族新成员,目前有动物实验显示IFN-λ1可清除小鼠上气道中的金黄色葡萄球菌,但其在人体的作用尚不明确。

为此,张罗教授团队选取正常人和CRSwNP患者鼻组织,构建金黄色葡萄球菌体外感染模型,比较IFN-λ1对二者细菌克隆数的影响,结果显示,IFN-λ1可显着降低正常鼻组织内金黄色葡萄球菌的数量。进一步研究发现,IFN-λ1可通过IL-28R–JAK–STAT1-ROS信号通路,增强巨噬细胞的吞噬功能,提高巨噬细胞吞噬和杀伤细菌的能力,加速鼻组织内细菌的清除,减少细菌的持续存在。然而,IFN-λ1却不能降低鼻息肉组织中细菌的数量,结合“鼻息肉组织内巨噬细胞吞噬功能缺陷”等以往结果,研究团队提出,IFN-λ1无法清除鼻息肉组织内细菌的主要原因是其无法通过巨噬细胞发挥作用。

该研究首次证实了IFN-λ1在人体正常鼻组织内具有清除细菌的作用,为临床上正常人同时抗细菌和病毒治疗提供了理论支持。对于CRSwNP患者,由于组织内巨噬细胞功能缺陷,单纯给予IFN-λ1不能起到清除细菌的作用,因此恢复息肉组织中巨噬细胞功能,减少鼻息肉内细菌病毒的数量,或将成为治疗慢性鼻窦炎伴鼻息肉的新思路。

原始出处:

Lan F,et al.IFN-λ1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps.J Allergy Clin Immunol. 2019 Apr;143(4):1416-1425.e4.

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    2019-04-28 膀胱癌
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    2019-04-28 bugit
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