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.

Detrimental role of IL-33/ST2 pathway sustaining a chronic eosinophil-dependent Th2 inflammatory response, tissue damage and parasite burden during Toxocara canis infection in mice

“…The activation of the IL-33/ST2 pathway has been previously studied in nematode infection. In infection with Strongyloides venezuelensis it is responsible for inducing pulmonary eosinophilic inflammation, maintaining airway hyperresponsiveness, Th2 response in the lungs and consequently may play a role in expelling the worms from the lungs[ 18 , 19 ]. Resende et al .…”

“…The activation of the IL-33/ST2 pathway has been previously studied in nematode infection. In infection with Strongyloides venezuelensis it is responsible for inducing pulmonary eosinophilic inflammation, maintaining airway hyperresponsiveness, Th2 response in the lungs and consequently may play a role in expelling the worms from the lungs [18,19]. Resende et al [6] observed high concentrations of IL-33 in BALB/c mice infected with T. canis from the 5th day after infection, however, the importance of activating the IL-33/ST2 pathway to control parasitic burden and pathophysiology in the context of T. canis infection has not yet been demonstrated.…”

The Relationship of Parasite Allergens to Allergic Diseases

“…Strongyloidiasis can be asymptomatic [ 30 ], but in some cases can elicit allergic respiratory or cutaneous manifestations. Murine models show that this parasite induces airway hyperreactivity with asthma-like characteristics, such as eosinophilic inflammation, mucus hypersecretion, and bronchial wall thickening [ 31 ]. In humans, the infection can manifest with chronic cough, mimic asthma exacerbations, or worsen stable asthma, thus complicating the evolution and management of this disease [ 32 , 33 •, 34 ].…”

Anticorpos IgY anti-larvas de Ancylostoma ceylanicum aplicados no imunodiagnóstico da ancilostomíase humana e reatividade cruzada com a estrongiloidíase

“…Nas formas moderada e grave podem ser reportados sinais e sintomas cutâneos, pulmonares, gastrointestinais, havendo predomínio de manifestações digestivas como mencionado acima. As manifestações são mais intensas nos casos de disseminação, aumento na secreção de muco, tendo como objetivo a eliminação do parasito(ARAUJO et al, 2016;BRELOER, ABRAHAM, 2016;NUTMAN, 2016;). Os hospedeiros infectados com Strongyloides sp.…”