Immunology Select

This issue's Immunology Select discusses recent studies on allergic responses in mouse models of human disease as well as how certain drugs, like the glucocorticoid dexamethasone, alleviate the symptoms of allergy. There are many similarities between the immune responses to allergens and to parasitic worms. In their new study, Reese et al. (2007) examined immune responses in the lung tissue of mice infected with the helminth Nippostrongylus brasiliensis. This parasitic worm migrates to the lung, where it molts and remodels its stiff pharyngeal feeding tube made of the biopolymer chitin before ascending the trachea and being swallowed, thereby enabling it to access the intestine. In this model of infection, the mammalian proteins acidic chitinase AMCase and Ym1 and Ym2 (chi-tinase-like proteins) are produced in response to the transcription factor Stat6. Reese et al. determined that there is Stat6-mediated production of AMCase and Ym2 in the lungs of mice at 3 days post worm infection. Given that AMCase is an enzymatically active chitinase, yet mammals lack chitin, the authors next examined whether the immune response could be mediated by the chitin discarded by the molting worms. They administered chitin intranasally to introduce it into the lungs of mice, which resulted in recruitment of eosinophils and basophils within 2 to 3 days. This recruitment was abrogated by pretreatment of the chitin with enzymatically active AMCase. They next generated mice that overexpressed AMCase constitutively in the lung. When exposed to chitin, these mice had lowered inflammatory responses. Interestingly, the recruitment of eosinophils and basophils is independent of Stat6 but is dependent on the eosinophil chemoattractant leukotriene B4 secreted by macrophages. The authors go on to show that a special type of macrophage (an alternatively activated macrophage) appears in the lung tissue upon exposure of mice to chitin. The authors propose a model in which macrophages encountering chitin become alternatively activated and secrete the chemoattractant leukotriene B4 in response to chitin in order to entice eosinophils to enter the tissue. Subsequent production of AMCase in response to interleukin (IL)-4 and IL-13 produced by inflammatory cells degrades the chitin, thereby attenuating the response. Given the ubiquitous nature of chitin in the environment (it provides structural rigidity to fungi, crustaceans, and insects as well as worms and their eggs) and the incidence of asthma in shellfish workers, chitin may be an important cause of allergy in humans. Xanthou et al. (2007) examine the role of the …