Type 2 Immunity Reflects Orchestrated Recruitment of Cells Committed to IL-4 Production

Abstract

Using IL-4 reporter mice we identified eosinophils, basophils, and Th2 cells as the three IL-4-producing cell types that appear in the lungs of mice infected with the migrating intestinal helminth, Nippostrongylus brasiliensis. Eosinophils were most prevalent, peaking by ∼1000-fold on day 9 after infection, with Th2 cells and basophils at 3- and 10-fold lower numbers, respectively. Eosinophil and basophil expansion in blood in response to parasites and their capacity for IL-4 expression required neither Stat6 nor T cells. Th2 induction and expansion in draining lymph nodes was also Stat6 independent. In contrast, eosinophil (and Th2 cell) recruitment to the lung was dependent on Stat6 expression by a bone marrow-derived tissue resident cell, whereas basophil recruitment was Stat6 and IL-4/IL-13 independent but T cell dependent. Primary type 2 immune responses in the lung represent the focal recruitment and activation of discrete cell populations from the blood that have previously committed to express IL-4.