Journal of Clinical Investigation -- Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks

Clin Invest. doi:10.1172/JCI42680.
Copyright © 2010, The American Society for Clinical Investigation.
Research Article
Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks
Takeshi Wada1, Kenji Ishiwata2, Haruhiko Koseki3, Tomoyuki Ishikura3, Tsukasa Ugajin1,4, Naotsugu Ohnuma1, Kazushige Obata1, Ryosuke Ishikawa1, Soichiro Yoshikawa1, Kaori Mukai1, Yohei Kawano1, Yoshiyuki Minegishi1,5, Hiroo Yokozeki4, Naohiro Watanabe2 and Hajime Karasuyama1,5

1Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
2Department of Tropical Medicine, Jikei University School of Medicine, Tokyo, Japan.
3Laboratory for Developmental Genetics, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
4Department of Dermatology and
5Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Tokyo Medical and Dental University Graduate School, Tokyo, Japan.

Address correspondence to: Hajime Karasuyama, Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Phone: 81.3.5803.5162; Fax: 81.3.3814.7172; E-mail: karasuyama.mbch@tmd.ac.jp.

Published July 26, 2010
Received for publication February 16, 2010, and accepted in revised form May 19, 2010.

Ticks are ectoparasitic arthropods that can transmit a variety of microorganisms to humans and animals during blood feeding, causing serious infectious disorders, including Lyme disease. Acaricides are pharmacologic agents that kill ticks. The emergence of acaricide-resistant ticks calls for alternative control strategies for ticks and tick-borne diseases. Many animals develop resistance to ticks after repeated infestations, but the nature of this acquired anti-tick immunity remains poorly understood. Here we investigated the cellular and molecular mechanisms underlying acquired resistance to Haemaphysalis longicornis ticks in mice and found that antibodies were required, as was IgFc receptor expression on basophils but not on mast cells. The infiltration of basophils at tick-feeding sites occurred during the second, but not the first, tick infestation. To assess the requirement for basophil infiltration to acquired tick resistance, mice expressing the human diphtheria toxin receptor under the control of the mast cell protease 8 (Mcpt8) promoter were generated. Diphtheria toxin administration to these mice selectively ablated basophils. Diphtheria toxin–mediated basophil depletion before the second tick infestation resulted in loss of acquired tick resistance. These data provide the first clear evidence, to our knowledge, that basophils play an essential and nonredundant role in antibody-mediated acquired immunity against ticks, which may suggest new strategies for controlling tick-borne diseases.

See the related Commentary Mice that “conditionally” lack basophils, AT LAST.

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Journal of Clinical Investigation -- Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks