Contribution of IL-18 to eosinophilic airway inflammation induced by immunization and challenge with Staphylococcus aureus proteins
Contribution of IL-18 to eosinophilic airway inflammation induced by immunization and challenge with Staphylococcus aureus proteins
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DOI：
10.1093/intimm/dxq040
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发表时间：
2010-07-01
影响因子：
4.4
通讯作者：
Nakanishi, Kenji
中科院分区：
文献类型：
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作者：
Kuroda-Morimoto, Mai;Tanaka, Hidehisa;Nakanishi, Kenji
我们以前报道过，用卵清蛋白（OVA）加IL-18鼻内激发可诱导具有OVA特异性T（h）1细胞的小鼠的气道高反应性（AHR）和嗜酸性粒细胞气道炎症。这两种病症可以分别通过中和抗IFN-γ和抗IL-13抗体来预防。在用OVA加LPS而不是IL-18攻击后，小鼠发展AHR和嗜酸性气道炎症，并且已知内源性IL-18参与其中。相比之下，IL-18不会促进具有OVA特异性T（h）2细胞的小鼠的这些变化。在这里，我们研究了IL-18是否参与了免疫小鼠和细菌蛋白激发的哮喘的发展。在鼻内暴露于来源于金黄色葡萄球菌的蛋白A（SpA）后，如果IFN-γ或IL-13分别存在，则用SpA免疫的小鼠表现出AHR和支气管周围嗜酸性粒细胞炎症。来自SpA免疫和攻击小鼠的引流淋巴结（DLN）的CD 4（+）T细胞产生了对固定的抗CD 3抗体的强烈的IFN-γ和IL-13应答。用中和性抗IL-18抗体治疗可预防哮喘炎症，同时降低表达IFN-γ和IL-13的能力。此外，接受来自SpA免疫小鼠DLN的CD 4（+）T细胞的幼稚小鼠根据IL-18的存在发展了气道炎症。接受SpA体外刺激的人PBMC的免疫缺陷小鼠，在SpA激发后出现了人CD 4（+）T细胞的密集支气管周围积聚。中和性抗人IL-18抗体保护对抗这种气道炎症。这些结果表明IL-18对于与气道暴露于细菌蛋白相关的哮喘炎症的发展的重要性。
We previously reported that intranasal challenge with ovalbumin (OVA) plus IL-18 induces airway hyperresponsiveness (AHR) and eosinophilic airway inflammation in mice with OVA-specific T(h)1 cells. These two conditions can be prevented by neutralizing anti-IFN-gamma and anti-IL-13 antibodies, respectively. The mice develop AHR and eosinophilic airway inflammation after challenge with OVA plus LPS instead of IL-18 and endogenous IL-18 is known to be involved. In contrast, IL-18 does not facilitate these changes in mice possessing OVA-specific T(h)2 cells. Here, we investigated whether IL-18 is involved in the development of asthma in mice immunized and challenged with bacterial proteins. Upon intranasal exposure to protein A (SpA) derived from Staphylococcus aureus, mice immunized with SpA exhibited AHR and peribronchial eosinophilic inflammation if IFN-gamma or IL-13 were present, respectively. The CD4(+) T cells from draining lymph nodes (DLNs) of the SpA-immunized and -challenged mice produced a robust IFN-gamma and IL-13 in response to immobilized anti-CD3 antibodies. Treatment with neutralizing anti-IL-18 antibodies prevented asthmatic inflammation concomitant with their impaired potential to express IFN-gamma and IL-13. Furthermore, naive mice that received the CD4(+) T cells from DLNs of SpA-immunized mice developed airway inflammation depending upon the presence of IL-18. Immunodeficient mice that received human PBMCs, which had been stimulated with SpA in vitro, developed dense peribronchial accumulation of human CD4(+) T cells upon SpA challenge. Neutralizing anti-human IL-18 antibodies protected against this airway inflammation. These results suggest the importance of IL-18 for the development of asthmatic inflammation associated with airway exposure to bacterial proteins.