Biology of the Eosinophilic Leukocyte

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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).