title: Impaired basophil induction leads to an age-dependent innate defect in type 2 immunity during helminth infection in mice.
abstract: Parasitic-infection studies on rhesus macaque monkeys have shown juvenile animals to be more susceptible to infection than adults, but the immunological mechanism for this is not known. In this study, we investigated the age-dependent genesis of helminth-induced type 2 immune responses using adult (6-8-wk-old) and juvenile (21-28-d-old) mice. Following infection with the parasitic nematode Nippostrongylus brasiliensis, juvenile mice had increased susceptibility to infection relative to adult mice. Juvenile mice developed a delayed type 2 immune response with decreased Th2 cytokine production, IgE Ab responses, mouse mast cell protease 1 levels, and intestinal goblet cell induction. This innate immune defect in juvenile mice was independent of TLR signaling, dendritic cells, or CD4(+) cell function. Using IL-4-eGFP mice, it was demonstrated that the numbers of IL-4-producing basophil and eosinophils were comparable in young and adult naive mice; however, following helminth infection, the early induction of these cells was impaired in juvenile mice relative to older animals. In nonhelminth models, there was an innate in vivo defect in activation of basophils, but not eosinophils, in juvenile mice compared with adult animals. The specific role for basophils in this innate defect in helminth-induced type 2 immunity was confirmed by the capacity of adoptively transferred adult-derived basophils, but not eosinophils, to restore the ability of juvenile mice to expel N. brasiliensis. The defect in juvenile mice with regard to helminth-induced innate basophil-mediated type 2 response is relevant to allergic conditions.
authors.affiliation: Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland.
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Nel
authors.forename: Emily
authors.initials: E
authors.lastname: Hams
authors.forename: Sean P
authors.initials: SP
authors.lastname: Saunders
authors.forename: Niamh E
authors.initials: NE
authors.lastname: Mangan
authors.forename: Philip
authors.initials: P
authors.lastname: Smith
authors.forename: Ann
authors.initials: A
authors.lastname: Atzberger
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Andrew N
authors.initials: AN
authors.lastname: McKenzie
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
mesh_terms: D000367:Age Factors; D000818:Animals; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D004198:Disease Susceptibility / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology* / Q000502:physiology; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: D020381:Interleukin-17; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; D049452:Green Fluorescent Proteins; D015847:Interleukin-4; D007371:Interferon-gamma