Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production.
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 approximately 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.
Voehringer
David
D
Howard Hughes Medical Institute, Department of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA.
Shinkai
Kanade
K
Locksley
Richard M
RM
D000818:Animals; D001491:Basophils / Q000166:cytology / Q000276:immunology; D002465:Cell Movement; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D049452:Green Fluorescent Proteins; D007249:Inflammation / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D018448:Models, Immunological; D009559:Nippostrongylus; D020411:Oligonucleotide Array Sequence Analysis; D050800:STAT6 Transcription Factor; D017206:Strongylida Infections / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology
D008164:Luminescent Proteins; D008565:Membrane Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D049452:Green Fluorescent Proteins; D015847:Interleukin-4