Abstract

Classical studies have shown that Aedes aegypti salivary secretion is responsible for the sensitization to mosquito bites and many of the components present in saliva are immunogenic and capable of inducing an intense immune response. Therefore, we have characterized a murine model of adjuvant-free systemic allergy induced by natural exposure to mosquito bites. BALB/c mice were sensitized by exposure to A. aegypti mosquito bites and intranasally challenged with phosphate-buffered saline only or the mosquito’s salivary gland extract (SGE). Blood, bronchoalveolar lavage (BAL) and lung were collected and evaluated for cellularity, histopathological analyses, cytokines and antibody determination. Respiratory pattern was analyzed by Penh measurements and tracheal segments were obtained to study in vitro reactivity to methacholine. BAL recovered from sensitized mice following challenge with SGE showed an increased number of eosinophils and Th2 cytokines such as IL-4, IL-5 and IL-13. Peribronchoalveolar eosinophil infiltration, mucus and collagen were also observed in lung parenchyma of sensitized mice, suggesting the development of a typical Th2 response. However, the antibody profile in serum of these mice evidenced a mixed-type response with presence of both, IgG1/IgE (Th2-related) and IgG2a (Th1-related) isotypes. In addition, changes in breathing pattern and tracheal reactivity to methacholine were not found. Taken together, our results show that A. aegypti bites trigger an atypical allergic reaction, with some classical cellular and soluble Th2 components in the lung, but also systemic Th1 and Th2 antibody isotypes and no change in either the respiratory pattern or the trachea responsiveness to agonist.

Highlights

  • Aedes aegypti is one of the most well characterized mosquito species in public health and the primary vector of arbovirus causing important diseases such as dengue fever, yellow fever, Chikungunya fever, and Zika fever in tropical areas [1,2]

  • The salivary secretion injected into the host skin during the blood feeding is rich in pharmacologically active substances that allow the mosquito to successfully feed by counteracting host hemostatic, inflammatory and immunological defenses [3,4,5,6], and it provides an essential vehicle for pathogen transmission to vertebrate hosts [7]

  • Mice naturally exposed to mosquitoes once (1x group) or four times (4x group) and challenged with salivary gland extract (SGE) demonstrated a significant increase in the recruitment of inflammatory cells to the airways compared with the control group (PBS-challenged mice), as observed by the total number of cells recovered from the bronchoalveolar lavage (BAL) (Fig 1B)

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Summary

Introduction

Aedes aegypti is one of the most well characterized mosquito species in public health and the primary vector of arbovirus causing important diseases such as dengue fever, yellow fever, Chikungunya fever, and Zika fever in tropical areas [1,2]. Mosquitoes that have had their main salivary duct cut are able to get a blood meal from a bitesensitized individual, but the bite does not cause cutaneous reactions as those observed for normal mosquitos [14]. Several allergens have been identified in mosquito whole extract, just a few present in the salivary glands of A. aegypti females have known functions in allergic response, namely Aed a 1 [15], Aed a 2 [16] and Aed a 3 [17]. All these allergens have been recognized by the IgE produced in mosquito-allergic subjects

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