IL-22-binding protein exacerbates influenza, bacterial super-infection.,Mucosal Immunology

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IL-22-binding protein exacerbates influenza, bacterial super-infection.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2019-07-11 , DOI: 10.1038/s41385-019-0188-7
Robert N Abood ₁ , Kevin J McHugh ₁ , Helen E Rich ₁ , Marianna A Ortiz ₁ , Joshua M Tobin ₁ , Krishnaveni Ramanan ₁ , Keven M Robinson ₂ , Jennifer M Bomberger ₃ , Jay K Kolls ₄ , Michelle L Manni ₁ , Derek A Pociask ₅ , John F Alcorn ₁

Affiliation

Secondary bacterial pneumonia is a significant complication of severe influenza infection and Staphylococcus aureus and Streptococcus pneumoniae are the primary pathogens of interest. IL-22 promotes S. aureus and S. pneumoniae host defense in the lung through epithelial integrity and induction of antimicrobial peptides and is inhibited by the soluble decoy receptor IL-22-binding protein (IL-22BP). Little is known about the effect of the IL-22/IL-22BP regulatory pathway on lung infection, and it has not been studied in the setting of super-infection. We exposed wild-type and IL-22BP-/- mice to influenza A/PR/8/34 for 6 days prior to infection with S. aureus (USA300) S. pneumoniae. Super-infected IL-22BP-/- mice had decreased bacterial burden and improved survival compared to controls. IL-22BP-/- mice exhibited decreased inflammation, increased lipocalin 2 expression, and deletion of IL-22BP was associated with preserved epithelial barrier function with evidence of improved tight junction stability. Human bronchial epithelial cells treated with IL-22Fc showed evidence of improved tight junctions compared to untreated cells. This study revealed that IL-22BP-/- mice are protected during influenza, bacterial super-infection, suggesting that IL-22BP has a pro-inflammatory role and impairs epithelial barrier function likely through interaction with IL-22.

中文翻译：

IL-22 结合蛋白会加剧流感和细菌重复感染。

继发性细菌性肺炎是严重流感感染的重要并发症，金黄色葡萄球菌和肺炎链球菌是主要病原体。 IL-22 通过上皮完整性和抗菌肽的诱导促进肺部金黄色葡萄球菌和肺炎链球菌宿主防御，并被可溶性诱饵受体 IL-22 结合蛋白 (IL-22BP) 抑制。关于IL-22/IL-22BP调节途径对肺部感染的影响知之甚少，并且尚未在重复感染的情况下进行研究。我们将野生型和 IL-22BP-/- 小鼠暴露于甲型/PR/8/34 流感病毒中 6 天，然后感染金黄色葡萄球菌 (USA300) 肺炎链球菌。与对照组相比，超级感染的 IL-22BP-/- 小鼠的细菌负荷减少，存活率提高。 IL-22BP-/- 小鼠表现出炎症减轻、脂质运载蛋白 2 表达增加，并且 IL-22BP 的缺失与保留的上皮屏障功能相关，有证据表明紧密连接稳定性得到改善。与未处理的细胞相比，用 IL-22Fc 处理的人支气管上皮细胞显示出紧密连接改善的证据。这项研究表明，IL-22BP-/- 小鼠在流感、细菌重复感染期间受到保护，表明 IL-22BP 具有促炎作用，并可能通过与 IL-22 相互作用损害上皮屏障功能。

更新日期：2019-11-18

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