Hookworm-Induced Persistent Changes to the Immunological Environment of the Lung

Infection with Nippostrongylus brasiliensis results in persistent changes to the lung environment. Cytokine profiling reveals a sustained increase in both Th1 and Th2 transcripts. Cellular populations of macrophages display an alternative phenotype, with upregulation of YM1, Arg1, Mrc1 as well as Class II MHC. These alternatively activated alveolar macrophages (AAAMs) also increase drastically in number. Subsequent challenge with house dust mite (HDM) Dermatophagoides pteronyssinus shows a reduced allergic phenotype, with decreased fold changes in effector cell cytokines of both the Th1 and Th2 variety indicative of the new regulatory environment established in the lung by helminth infection. Histological examination of the lung environment reveals a significant decrease in eosinophila and reduced mucous production by bronchial epithelial cells. Keywords: Timecourse, Infection, Allergy Model BALB/c mice were challenged with 500 infectious L3 stage Nippostrongylus brasiliensis larvae subcutaneously. Mice were allowed to resolve their infection, then were sensitized twice with 75 allergy units (AU) of HDM bound to 1mg of alum intraperitoneally. Two challenge doses of 50AU HDM in PBS were given intranasally one day apart, then lungs were harvested at 6, 24 and 72 hours post challenge. Mice were analyzed by histology, immunohistochemistry, real time RT-PCR and affymetrix gene array analysis using full genome chips.