Pulmonary immune cells and inflammatory cytokine dysregulation are associated with mortality of IL-1R1-/- mice infected with influenza virus (H1N1)
Pulmonary immune cells and inflammatory cytokine dysregulation are associated with mortality of IL-1R1-/- mice infected with influenza virus (H1N1)
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肺部免疫细胞和炎症细胞因子失调与感染流感病毒（H1N1）的 IL-1R1-/- 小鼠的死亡率相关
DOI：
10.24272/j.issn.2095-8137.2017.035
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发表时间：
2017-05-18
影响因子：
4.9
通讯作者：
Liu, Long-Ding
中科院分区：
文献类型：
--
作者：
Guo, Lei;Wang, Yan-Cui;Liu, Long-Ding
呼吸道病毒感染可引起病毒性肺炎和急性肺损伤（ALI）。白细胞介素-1 (IL-1) 家族由促炎性细胞因子组成，在调节体内免疫和炎症反应中发挥重要作用。IL-1 信号传导通过介导肺部抗病毒免疫反应和炎症来预防呼吸道流感病毒感染。我们分析了导致致命性 H1N1 病毒感染的 IL-1 受体 1 (IL-1R1) 缺陷小鼠的炎症性肺部病理学和死亡的浸润肺免疫白细胞和细胞因子。结果显示，与野生型感染小鼠相比，观察到早期先天免疫细胞和细胞因子/趋化因子失调，感染IL-1R1(-/-)小鼠的中性粒细胞浸润以及支气管肺泡灌洗液中IL-6、TNF-α、G-CSF、KC和MIP-2细胞因子水平显着降低。 IL-1R1(-/-) 小鼠中针对 H1N1 病毒的适应性免疫反应因抗病毒 Th1 细胞、CD8+ 细胞和抗体功能下调而受损，从而导致病毒清除减弱。组织学分析显示，与WT感染小鼠相比，IL-1R1(-/-)小鼠早期感染期间肺部炎症减轻，但晚期感染期间肺部病理严重。此外，受感染的IL-1R1(-/-)小鼠表现出骨髓中中性粒细胞生成显着减少，并且中性粒细胞向发炎的肺部募集。总之，这些结果表明 IL-1 信号传导与肺部抗流感免疫反应和炎症性肺损伤相关，特别是通过对中性粒细胞动员和炎症细胞因子/趋化因子产生的影响。
Respirovirus infection can cause viral pneumonia and acute lung injury (ALI). The interleukin-1 (IL-1) family consists of proinflammatory cytokines that play essential roles in regulating immune and inflammatory responses in viva IL-1 signaling is associated with protection against respiratory influenza virus infection by mediation of the pulmonary anti-viral immune response and inflammation. We analyzed the infiltration lung immune leukocytes and cytokines that contribute to inflammatory lung pathology and mortality of fatal H1N1 virus-infected IL-1 receptor 1 (IL-1R1) deficient mice. Results showed that early innate immune cells and cytokine/chemokine dysregulation were observed with significantly decreased neutrophil infiltration and IL-6, TNF-alpha, G-CSF, KC, and MIP-2 cytokine levels in the bronchoalveolar lavage fluid of infected IL-1R1(-/-) mice in comparison with that of wild type infected mice. The adaptive immune response against the H1N1 virus in IL-1R1(-/-) mice was impaired with downregulated anti-viral Th1 cell, CD8+ cell, and antibody functions, which contributes to attenuated viral clearance. Histological analysis revealed reduced lung inflammation during early infection but severe lung pathology in late infection in IL-1R1(-/-) mice compared with that in WT infected mice. Moreover, the infected IL-1R1(-/-) mice showed markedly reduced neutrophil generation in bone marrow and neutrophil recruitment to the inflamed lung. Together, these results suggest that IL-1 signaling is associated with pulmonary anti-influenza immune response and inflammatory lung injury, particularly via the influence on neutrophil mobilization and inflammatory cytokine/chemokine production.