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 1

IgFc receptors on mast cells are dispensable for antibody-mediated, protective immunity against ticks.

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IgFc receptors on mast cells are dispensable for antibody-mediated, prot...
(A) C57BL/6 and (B) C57BL/6-KitW-sh/W-sh mice were infested with larval H. longicornis ticks once or twice at an interval of 14 days. The relative tick repletion in each experimental group is shown, in that the value in the first infestation was defined as 100%. Data are shown as mean ± SEM, n = 5 (A); n = 4 (B). (C) BMMCs derived from wild-type mice were adoptively transferred to KitW-sh/W-sh mice, and the recipient mice were infested and analyzed as in A. Data are shown as mean ± SEM, n = 3 each. (D) μMT and (E) Fcer1g–/– C57BL/6 mice were infested with ticks as in A, and the relative tick repletion in each group is shown. Data are shown as mean ± SEM, n = 5 (D); n = 4 (E). (F) BMMCs derived from Fcer1g–/– mice were adoptively transferred to KitW-sh/W-sh mice, and the recipient mice were infested and analyzed as in A. Data are shown as mean ± SEM, n = 3 each. Data shown in A–F are representative of at least 3 repeated experiments. **P < 0.01.