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Allergen-Specific Treg Cells Upregulated by Lung-Stage S. japonicum Infection Alleviates Allergic Airway Inflammation.

ABSTRACT: Schistosoma japonicum infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of the helminth infection and the underlying mechanisms. Most previous studies focused on understanding the preventive effect of S. japonicum infection on asthma (infection before allergen sensitization), whereas the protective effects of S. japonicum infection (allergen sensitization before infection) on asthma were rarely investigated. In this study, we investigated the protective effects of S. japonicum infection on AAI using a mouse model of OVA-induced asthma. To explore how the timing of S. japonicum infection influences its protective effect, the mice were percutaneously infected with cercaria of S. japonicum at either 1 day (infection at lung-stage during AAI) or 14 days before ovalbumin (OVA) challenge (infection at post-lung-stage during AAI). We found that lung-stage S. japonicum infection significantly ameliorated OVA-induced AAI, whereas post-lung-stage infection did not. Mechanistically, lung-stage S. japonicum infection significantly upregulated the frequency of regulatory T cells (Treg cells), especially OVA-specific Treg cells, in lung tissue, which negatively correlated with the level of OVA-specific immunoglobulin E (IgE). Depletion of Treg cells in vivo partially counteracted the protective effect of lung-stage S. japonicum infection on asthma. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage S. japonicum infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage S. japonicum infection could relieve OVA-induced asthma in a mouse model. The protective effect was mediated by the upregulated OVA-specific Treg cells, which suppressed IgE production. Our results may facilitate the discovery of a novel therapy for AAI.

SUBMITTER: Li Z

PROVIDER: S-EPMC8217774 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionExcretory/secretory products (ESPs) derived from helminths have been reported to effectively control allergic inflammation, which have better therapeutic prospects than live parasite infections. However, it remains unknown whether ESPs from schistosome eggs can protect against allergies, despite reports alleging that schistosome infection could alleviate disordered allergic inflammation.MethodIn the present study, we investigated the protective effects of ESPs from Schistosoma japonicum eggs (ESP-SJE) on asthmatic inflammation. Firstly, we successfully established an allergic airway inflammation model in mice by alum-adjuvanted ovalbumin (OVA) sensitization and challenge. ESP-SJE were administered intraperitoneally on days -1 and 13 (before sensitization), on day 20 (before challenge), and on days 21-24 (challenge phase).ResultsThe results showed that ESP-SJE treatment significantly reduced the infiltration of inflammatory cells, especially eosinophils into the lung tissue, inhibited the production of the total and OVA-specific IgE during OVA-sensitized and -challenged phases, respectively, and suppressed the secretion of Th2-type inflammatory cytokines (IL-4). Additionally, ESP-SJE treatment significantly upregulated the regulatory T cells (Tregs) in the lung tissue during OVA challenge. Furthermore, using liquid chromatography-mass spectrometry analysis and Treg induction experiments in vitro, we might identify nine potential therapeutic proteins against allergic inflammation in ESP-SJE. The targets of these candidate proteins included glutathione S-transferase, egg protein CP422 precursor, tubulin alpha-2/alpha-4 chain, actin-2, T-complex protein 1 subunit beta, histone H₄, whey acidic protein core region, and molecular chaperone HtpG.ConclusionTaken together, the results discussed herein demonstrated that ESP-SJE could significantly alleviate OVA-induced asthmatic inflammation in a murine model, which might be mediated by the upregulation of Treg in lung tissues that may be induced by the potential modulatory proteins. Therefore, potential proteins in ESP-SJE might be the best candidates to be tested for therapeutic application of asthma, thus pointing out to a possible new therapy for allergic airway inflammation.

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Allergen-Specific Treg Cells Upregulated by Lung-Stage S. japonicum Infection Alleviates Allergic Airway Inflammation.

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