Exposure to Aedes aegypti Bites Induces a Mixed-Type Allergic Response following Salivary Antigens Challenge in Mice

PLoS One. 2016 May 20;11(5):e0155454. doi: 10.1371/journal.pone.0155454. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aedes / immunology*
  • Allergens / immunology
  • Animals
  • Antibodies / metabolism
  • Cytokines / metabolism
  • Female
  • Flow Cytometry
  • Hypersensitivity / immunology*
  • Insect Bites and Stings / immunology*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Salivary Glands / immunology*

Substances

  • Allergens
  • Antibodies
  • Cytokines
  • Interleukin-5
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma

Grants and funding

This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2009/07208-0 and 2009/09892-6), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 302194/2009-6 and 472536/2012-5) and Research Network on Bioactive Molecules from Arthropod Vectors from University of Sao Paulo (NAP-MOBIARVE 12.1.17661.1.7). The following authors were recipients of fellowships: MSB (CNPq 134660/2010-2); DIG (FAPESP 2011/06626-3); ADR (FAPESP 2011/22669-4); BB (FAPESP 2009/12247-5); CNL (FAPESP 2011/15569-3); CM (FAPESP 2010/18216-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.