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.

Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion

“…In the past few years nonredundant protective functions of basophils have been observed during secondary infections with helminths and ticks (13,14,17). However, the underlying mechanisms remained poorly understood.…”

“…Over the past years several genetic mouse models have been used to elucidate basophil functions in vivo. It has been shown that basophils cooperate with dendritic cells to initiate Th2 responses, promote alternative activation of macrophages, and contribute to acquired resistance against parasites (12)(13)(14)(15)(16). We and others have shown that basophils contribute to protective immune responses against secondary infection by Nb and ticks (13,14,17).…”

Protective Role of STAT6 in Basophil-Dependent Prurigo-like Allergic Skin Inflammation

“…However, in some inflammatory conditions, basophils are recruited to the skin (15). Although they share morphological and functional similarities with mast cells, basophils have unique functions; for example, in addition to producing IL-4 and IL-13 (16)(17)(18), they play important roles in acquired immunity against helminths and ticks and in IgGdependent anaphylactic reactions (19)(20)(21). Thus, certain allergic events, in particular Th2-type immune responses, are likely involved in the pathogenesis of prurigo, although the details of the underlying mechanism have not been clearly defined.…”

Role of Mast Cells and Basophils in IgE Responses and in Allergic Airway Hyperresponsiveness

“…A knock-in system of the diphtheria toxin receptor (DTR) gene into the Mcpt8 locus is another promising tool that was recently established (15). However, there is still a need for tools to precisely distinguish and investigate MC and basophil functions in the same experimental system.…”