Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks
Takeshi Wada, … , Naohiro Watanabe, Hajime Karasuyama
Takeshi Wada, … , Naohiro Watanabe, Hajime Karasuyama
Published July 26, 2010
Citation Information: J Clin Invest. 2010;120(8):2867-2875. https://doi.org/10.1172/JCI42680.
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Research Article

Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks

Abstract

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.

Authors

Takeshi Wada, Kenji Ishiwata, Haruhiko Koseki, Tomoyuki Ishikura, Tsukasa Ugajin, Naotsugu Ohnuma, Kazushige Obata, Ryosuke Ishikawa, Soichiro Yoshikawa, Kaori Mukai, Yohei Kawano, Yoshiyuki Minegishi, Hiroo Yokozeki, Naohiro Watanabe, Hajime Karasuyama

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Figure 6

IgFc receptors on basophils are essential for antibody-mediated, protective immunity against ticks.

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IgFc receptors on basophils are essential for antibody-mediated, protect...
(A) The CD49b+ basophil–enriched fraction of splenocytes from C57BL/6 mice infested only once (sensitized) or never (naive) was adoptively transferred into naive, uninfested C57BL/6 mice, and 2 hours later, the recipient mice were infested with ticks. The relative tick repletion for each group is shown. The value for the control, vehicle-treated mice was defined as 100%. Data are shown as mean ± SEM, n = 3 each. (B) The basophil-enriched fraction of splenocytes from DT- or PBS-treated Mcpt8DTR mice that had been infested once was adoptively transferred into naive, uninfested littermate control mice. The recipient mice were then infested, and the relative tick repletion is shown as in A. Data are shown as mean ± SEM, n = 3 each. (C) The basophil-enriched fraction of splenocytes from wild-type or Fcer1g–/– mice that had been infested once was adoptively transferred into naive, uninfested C57BL/6 mice, which were then infested. The relative tick repletion is shown as in A. Data are shown as mean ± SEM, n = 3 each. Data shown in A–C are representative of at least 3 repeated experiments. **P < 0.01.