Biology of the Eosinophilic Leukocyte

在本报告年度，我们继续探索嗜酸性粒细胞及其与呼吸道病毒病原体的相互作用。我们的第一项主要研究是与纽卡斯尔大学和澳大利亚新南威尔士大学的同事合作进行的，直接解决了这些问题。利用我们实验室开发的小鼠肺炎病毒（PVM）感染模型，我们研究了新生儿病毒感染和抗原暴露与嗜酸性粒细胞募集和其他过敏性哮喘标志的相互作用。在我们的研究结果中，我们观察到过敏性气道炎症，包括嗜酸性粒细胞的募集，在过敏原攻击前从新生儿感染PVM恢复的小鼠中最为突出。此外，从新生儿感染中恢复并表现出明显嗜酸性粒细胞增多的小鼠也表现出增强的th2偏倚免疫反应，包括血清抗卵清蛋白IgE和IgG1水平升高，以及th2相关细胞因子IL-4、IL-5和IL-13的相对表达增加。总的来说，我们得出结论，早期病毒感染和过敏原致敏/挑战共同促进儿童哮喘的特征，包括嗜酸性粒细胞募集和th2偏倚免疫反应（Siegle JS等，Respir Res 2010）。

During this reporting year, we have continued our exploration of eosinophils and their interactions with respiratory virus pathogens. Our first major study, performed in collaboration with colleagues at The University of Newcastle and The University of New South Wales, Australia, addresses these questions directly. Using the pneumonia virus of mice (PVM) infection model developed by our laboratory, we examine the interplay of neonatal virus infection and antigen exposure in relation to eosinophil recruitment and other hallmark signs of allergic asthma. Among our findings, we observed that allergic airway inflammation, including recruitment of eosinophils, was most prominent in mice that had recovered from neonatal infection with PVM prior to allergen challenge. Furthermore, the mice that recovered from neonatal infection and displayed significant eosinophilia also exhibited an augmented Th2-biased immune response, including elevated serum levels of anti-ovalbumin IgE and IgG1 as well as increased relative expression of Th2-associated cytokines IL-4, IL-5 and IL-13. Overall, we concluded that early-life viral infection and allergen sensitization/challenge together function to promote characteristic features of childhood asthma, including eosinophil recruitment and a Th2-biased immune response (Siegle JS et al., Respir Res 2010) Our second major study on this topic focused the interactions of isolated eosinophils with platelet-activating factor (PAF), a phospholipid mediator released from activated macrophages, mast cells, and basophils that promotes pathophysiologic responses, systemic inflammation and anaphylaxis. Eosinophil responses to PAF and to severe systemic responses are complex but remain incompletely elucidated. Using both wild-type and PAF receptor gene-deleted mouse eosinophils cultured from bone marrow as per the methods developed by our laboratory (as described in Dyer et al. J. Immunol. 2008) we found that PAF, lysoPAF and related phospholipids activate mouse eosinophils, but they do so via mechanisms that are surprisingly independent of the characterized PAF receptor. The nature of the novel receptor and signaling pathway awaits further characterization (Dyer et al., J. Immunol 2010).