title: The skin is an important bulwark of acquired immunity against intestinal helminths.
abstract: Once animals have experienced a helminthic infection, they often show stronger protective immunity against subsequent infections. Although helminthic infections are well known to elicit Th2-type immune responses, it remains ill-defined where and how acquired protection is executed. Here we show that skin-invading larvae of the intestinal helminth Nippostrongylus brasiliensis are surrounded by skin-infiltrating cells and are prevented from migrating out of infected skin during the second but not the first infection. B cell- or IgE receptor FcεRI-deficient mice showed impaired larval trapping in the skin. Selective ablation of basophils, but not mast cells, abolished the larval trapping, leading to increased worm burden in the lung and hence severe lung injury. Skin-infiltrating basophils produced IL-4 that in turn promoted the generation of M2-type macrophages, leading to the larval trapping in the skin through arginase-1 production. Basophils had no apparent contribution to worm expulsion from the intestine. This study thus reveals a novel mode of acquired antihelminth immunity, in which IgE-armed basophils mediate skin trapping of larvae, thereby limiting lung injury caused by larval migration.
authors.affiliation: Department of Immune Regulation, 2 Department of Environmental Parasitology, 3 Department of Integrated Pulmonology, and 4 Japan Science and Technology Agency Core Research for Evolutional Science and Technology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Obata-Ninomiya
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nei
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yoshikawa
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawano
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Minegishi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ohta
authors.forename: Naohiro
authors.initials: N
authors.lastname: Watanabe
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kanuka
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D001491:Basophils / Q000276:immunology / Q000469:parasitology; D007411:Intestinal Diseases, Parasitic / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D007814:Larva / Q000276:immunology; D055370:Lung Injury / Q000276:immunology / Q000469:parasitology; D008264:Macrophages / Q000145:classification / Q000276:immunology / Q000469:parasitology; D008407:Mast Cells / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology* / Q000472:pathogenicity*; D059208:Parasite Load; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000469:parasitology*; D017206:Strongylida Infections / Q000235:genetics / Q000276:immunology* / Q000469:parasitology
chemical_list: D000909:Antibodies, Helminth; C485701:Fcgr1 protein, mouse; D017452:Receptors, IgG; C544448:Arg1 protein, mouse; D001119:Arginase