TY - JOUR
T1 - Exposure to Aedes aegypti Bites Induces a Mixed-Type Allergic Response following Salivary Antigens Challenge in Mice
AU - Barros, Michele S.
AU - Gomes, Eliane
AU - Gueroni, Daniele I.
AU - Ramos, Anderson D.
AU - Mirotti, Luciana
AU - Florsheim, Esther
AU - Bizzarro, Bruna
AU - Lino, Ciro N.R.
AU - Maciel, Ceres
AU - Lino-Dos-Santos-Franco, Adriana
AU - Tavares-de-Lima, Wothan
AU - Capurro, Margareth L.
AU - Russo, Momtchilo
AU - Sá-Nunes, Anderson
N1 - Funding Information:
This work was supported by grants from Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo (FAPESP 2009/07208-0 and 2009/09892-6), Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (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.
Publisher Copyright:
© 2016 Barros et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/5
Y1 - 2016/5
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0155454
DO - 10.1371/journal.pone.0155454
M3 - Article
C2 - 27203689
AN - SCOPUS:84971280880
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 5
M1 - e0155454
ER -