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Contribution of IL-18 to eosinophilic airway inflammation induced by immunization and challenge with Staphylococcus aureus proteins

2010; Oxford University Press; Volume: 22; Issue: 7 Linguagem: Inglês

10.1093/intimm/dxq040

1460-2377

Mai Kuroda-Morimoto, Hidehisa Tanaka, Nobuki Hayashi, Masakiyo Nakahira, Yasutomo Imai, Michiko Imamura, Koubun Yasuda, Shizue Yumikura-Futatsugi, Kiyoshi Matsui, Toshihiro Nakashima, Kazuhisa Sugimura, Hiroko Tsutsui, Hajime Sano, Kenji Nakanishi,

Eosinophilic Esophagitis

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 Th1 cells. These two conditions can be prevented by neutralizing anti-IFN-γ 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 Th2 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-γ 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-γ 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-γ 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.