The role of IL-33/ST2, IL-4, and eosinophils on the airway hyperresponsiveness induced by Strongyloides venezuelensis in BALB/c mice.
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.
Departamento de Parasitologia Bloco Q3-sala 242, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antonio Carlos 6627, Campus Pampulha, Belo Horizonte, MG, Brazil, 31270-901.
Emilia Souza
ES
Araujo
Departamento de Parasitologia Bloco Q3-sala 242, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antonio Carlos 6627, Campus Pampulha, Belo Horizonte, MG, Brazil, 31270-901.
Cintia Aparecida
CA
de Jesus Pereira
Departamento de Parasitologia Bloco Q3-sala 242, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antonio Carlos 6627, Campus Pampulha, Belo Horizonte, MG, Brazil, 31270-901.
Ana Terezinha
AT
de Moura Pereira
Departamento de Parasitologia Bloco Q3-sala 242, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antonio Carlos 6627, Campus Pampulha, Belo Horizonte, MG, Brazil, 31270-901.
João Marcelo Peixoto
JM
Moreira
Departamento de Parasitologia Bloco Q3-sala 242, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antonio Carlos 6627, Campus Pampulha, Belo Horizonte, MG, Brazil, 31270-901.
Michelle Carvalho
MC
de Rezende
Departamento de Parasitologia Bloco Q3-sala 242, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antonio Carlos 6627, Campus Pampulha, Belo Horizonte, MG, Brazil, 31270-901.
Jailza Lima
JL
Rodrigues
Departamento de Bioquímica e Imunologia, ICB-UFMG, Belo Horizonte, MG, Brazil.
Mauro Martins
MM
Teixeira
Departamento de Parasitologia Bloco Q3-sala 242, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antonio Carlos 6627, Campus Pampulha, Belo Horizonte, MG, Brazil, 31270-901. denegrao@icb.ufmg.br.
Deborah
D
Negrão-Corrêa
D000485:Allergens / Q000276:immunology; D000818:Animals; D004802:Eosinophilia / Q000276:immunology / Q000469:parasitology; D004804:Eosinophils / Q000276:immunology*; D050982:GATA1 Transcription Factor / Q000235:genetics; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000235:genetics / Q000276:immunology*; D000067596:Interleukin-33 / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000469:parasitology; D013321:Strongyloides / Q000276:immunology*; D013322:Strongyloidiasis / Q000276:immunology* / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015848:Interleukin-5; D015847:Interleukin-4
Airway hyperresponsiveness; IL-33/ST2 pathway; IL-4 and eosinophils; Strongyloides venezuelensis