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

Kazushige Obata-Ninomiya, Kenji Ishiwata, Hidemitsu Tsutsui, Yuichiro Nei, Soichiro Yoshikawa, Yohei Kawano, Yoshiyuki Minegishi, Nobuo Ohta, Naohiro Watanabe, Hirotaka Kanuka, Hajime Karasuyama

Research output: Contribution to journalArticle

76 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2583-2595
Number of pages13
JournalJournal of Experimental Medicine
Volume210
Issue number12
DOIs
Publication statusPublished - Nov 1 2013
Externally publishedYes

Fingerprint

Helminths
Adaptive Immunity
Basophils
Skin
Lung Injury
Infection
Larva
Nippostrongylus
IgE Receptors
Arginase
Mast Cells
Interleukin-4
Immunoglobulin E
Intestines
Immunity
B-Lymphocytes
Macrophages
Lung

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Obata-Ninomiya, K., Ishiwata, K., Tsutsui, H., Nei, Y., Yoshikawa, S., Kawano, Y., ... Karasuyama, H. (2013). The skin is an important bulwark of acquired immunity against intestinal helminths. Journal of Experimental Medicine, 210(12), 2583-2595. https://doi.org/10.1084/jem.20130761

The skin is an important bulwark of acquired immunity against intestinal helminths. / Obata-Ninomiya, Kazushige; Ishiwata, Kenji; Tsutsui, Hidemitsu; Nei, Yuichiro; Yoshikawa, Soichiro; Kawano, Yohei; Minegishi, Yoshiyuki; Ohta, Nobuo; Watanabe, Naohiro; Kanuka, Hirotaka; Karasuyama, Hajime.

In: Journal of Experimental Medicine, Vol. 210, No. 12, 01.11.2013, p. 2583-2595.

Research output: Contribution to journalArticle

Obata-Ninomiya, K, Ishiwata, K, Tsutsui, H, Nei, Y, Yoshikawa, S, Kawano, Y, Minegishi, Y, Ohta, N, Watanabe, N, Kanuka, H & Karasuyama, H 2013, 'The skin is an important bulwark of acquired immunity against intestinal helminths', Journal of Experimental Medicine, vol. 210, no. 12, pp. 2583-2595. https://doi.org/10.1084/jem.20130761
Obata-Ninomiya, Kazushige ; Ishiwata, Kenji ; Tsutsui, Hidemitsu ; Nei, Yuichiro ; Yoshikawa, Soichiro ; Kawano, Yohei ; Minegishi, Yoshiyuki ; Ohta, Nobuo ; Watanabe, Naohiro ; Kanuka, Hirotaka ; Karasuyama, Hajime. / The skin is an important bulwark of acquired immunity against intestinal helminths. In: Journal of Experimental Medicine. 2013 ; Vol. 210, No. 12. pp. 2583-2595.
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