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The role of IL-33/ST2, IL-4, and eosinophils on the airway hyperresponsiveness induced by Strongyloides venezuelensis in BALB/c mice

Abstract

Strongyloidiasis is a neglected chronic nematode infection, in which the control of autoinfection rate and severity of disease is dependent on type 2 immune responses. Strongyloides also causes Th2 responses in the lung of infected animals and changes in airway function, including airway hyperresponsiveness (AHR). Mechanisms of AHR during Strongyloides venezuelensis infection are not entirely known, and we investigate here the role of IL-4, eosinophils, and IL-33/ST2. AHR was evaluated in infected mice by determining changes in lung function after increasing doses of methacholine. Balb/C, but no C57Bl/6, mice developed AHR, tissue eosinophilia, and increased local IL-4 and IL-5 production. Functional changes peaked at day 4 and 7, after the larva had left the lungs. AHR was clearly dependent on IL-4 but not on eosinophils, as evaluated by experiments in IL-4 and Gata-1-deficient mice. Experiments in ST2-deficient mice showed that this pathway was not needed for induction of AHR but was necessary for the maintenance of AHR and for Th2 responses in the lung. These studies clearly show a crucial role for IL-4 in the induction of AHR following S. venezuelensis infection and for IL-33/ST2 in maintaining AHR and lung Th2 responses.

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Acknowledgments

This study received financial support from the Fundação de Amparo a Pesquisas do Estado de Minas Gerais (FAPEMIG) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-Brazil, Basic Parasitology Program).

Authors’ contribution

Conceived of or designed the study: ESA, CAJP, MMT, and DNC

Performed parasitological and histopathological experiments: ESA, CAJP, JRL, MCR, JMPM, and DNC.

Optimized the methodology and performed AHR in infected animals: ESA, CAJP, ATMP, and MMT

Analyzed data: ESA and DNC

Wrote the manuscript: ESA, MMT, and DNC

The authors read and approved the final manuscript.

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Correspondence to Deborah Negrão-Corrêa.

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Competing interest

The authors declare no conflicts of interest.

Additional information

In memoriam of Ana Terezinha de Moura Pereira

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Araujo, E.S., de Jesus Pereira, C.A., de Moura Pereira, A.T. et al. The role of IL-33/ST2, IL-4, and eosinophils on the airway hyperresponsiveness induced by Strongyloides venezuelensis in BALB/c mice. Parasitol Res 115, 3107–3117 (2016). https://doi.org/10.1007/s00436-016-5066-6

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Keywords

  • Strongyloides venezuelensis
  • Airway hyperresponsiveness
  • IL-33/ST2 pathway
  • IL-4 and eosinophils