title: Basophils are the major producers of IL-4 during primary helminth infection.
abstract: IL-4 production by leukocytes is a key regulatory event that occurs early in the type 2 immune response, which induces allergic reactions and mediates expulsion of parasites. CD4(+) T cells and basophils are thought to be the key cell types that produce IL-4 during a type 2 response. In this study, we assessed the relative contribution of both CD4(+) T cell- and basophil-IL-4 production during primary and secondary responses to Nippostrongylus brasiliensis using a murine IL-4-enhanced GFP reporter system. During infection, IL-4-producing basophils were detected systemically, and tissue recruitment occurred independent of IL-4/STAT6 signaling. We observed that basophil recruitment to a tissue environment was required for their full activation. Basophil induction in response to secondary infection exhibited accelerated kinetics in comparison with primary infection. However, total basophil numbers were not enhanced, as predicted by previous models of protective immunity. Overall, the induction and migration of IL-4-producing basophils into peripheral tissues was found to be a prominent characteristic of the primary but not memory responses to N. brasiliensis infection, in which CD4(+) T cells were identified as the major source of IL-4. Whereas basophils were the major initial producers of IL-4, we determined that normal Th2 differentiation occurs independently of basophils, and depletion of basophils led to an enhancement of inflammatory cell recruitment to the site of infection.
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand. vanpanhuysn@niaid.nih.gov
authors.forename: Nicholas
authors.initials: N
authors.lastname: van Panhuys
authors.forename: Melanie
authors.initials: M
authors.lastname: Prout
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Forbes
authors.forename: Booki
authors.initials: B
authors.lastname: Min
authors.forename: William E
authors.initials: WE
authors.lastname: Paul
authors.forename: Graham
authors.initials: G
authors.lastname: Le Gros
mesh_terms: D000818:Animals; D001491:Basophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques; D007156:Immunologic Memory / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D008174:Lung Diseases, Parasitic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009559:Nippostrongylus / Q000276:immunology*; D050800:STAT6 Transcription Factor / Q000172:deficiency / Q000235:genetics; D017206:Strongylida Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4