The skin is an important bulwark of acquired immunity against intestinal helminths

Author:

Obata-Ninomiya Kazushige11,Ishiwata Kenji2,Tsutsui Hidemitsu1,Nei Yuichiro1,Yoshikawa Soichiro1,Kawano Yohei1,Minegishi Yoshiyuki11,Ohta Nobuo1,Watanabe Naohiro2,Kanuka Hirotaka2,Karasuyama Hajime11

Affiliation:

1. Department of Immune Regulation, Department of Environmental Parasitology, Department of Integrated Pulmonology, and 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

2. Department of Tropical Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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