S. mansoni -derived omega-1 prevents OVA-specific allergic airway inflammation via hampering of cDC2 migration
Chronic infection with Schistosoma mansoni parasites is associated with reduced allergic sensitization in humans, while schistosome eggs protects against allergic airway inflammation (AAI) in mice. One of the main secretory/excretory molecules from schistosome eggs is the glycosylated T2-RNAse Omega-1 (ω1). We hypothesized that ω1 induces protection against AAI during infection. Peritoneal administration of ω1 prior to sensitization with Ovalbumin (OVA) reduced airway eosinophilia and pathology, and OVA-specific Th2 responses upon challenge, independent from changes in regulatory T cells. ω1 was taken up by monocyte-derived dendritic cells, mannose receptor (CD206)-positive conventional type 2 dendritic cells (CD206+ cDC2), and by recruited peritoneal macrophages. Additionally, ω1 impaired CCR7, F-actin, and costimulatory molecule expression on myeloid cells and cDC2 migration in and ex vivo, as evidenced by reduced OVA+ CD206+ cDC2 in the draining mediastinal lymph nodes (medLn) and retainment in the peritoneal cavity, while antigen processing and presentation in cDC2 were not affected by ω1 treatment. Importantly, RNAse mutant ω1 was unable to reduce AAI or affect DC migration, indicating that ω1 effects are dependent on its RNAse activity. Altogether, ω1 hampers migration of OVA+ cDC2 to the draining medLn in mice, elucidating how ω1 prevents allergic airway inflammation in the OVA/alum mouse model.
Authors
- Frank Otto (ORCID: https://orcid.org/0000-0002-8648-2260)
- Hamida Hammad (ORCID: https://orcid.org/0000-0003-3762-8603)
- A. Schots (ORCID: https://orcid.org/0000-0002-6036-7088)
- Maria Yazdanbakhsh (ORCID: https://orcid.org/0000-0002-7666-1441)
- Yolanda van Wijck (ORCID: https://orcid.org/0000-0003-4384-736X)
- Bruno Guigas (ORCID: https://orcid.org/0000-0002-8856-5799)
- Christian Taube (ORCID: https://orcid.org/0000-0002-3546-1398)
- Thomas A. Gasan (ORCID: https://orcid.org/0000-0001-5240-4339)
- Hermelijn H. Smits (ORCID: https://orcid.org/0000-0001-9279-2890)
- Thiago A. Patente (ORCID: https://orcid.org/0000-0001-9333-869X)
- Cornelis H. Hokke (ORCID: https://orcid.org/0000-0003-3545-7804)
- Karl Vergote
- Stijn Verwaerde (ORCID: https://orcid.org/0000-0002-1398-8746)
- Ruud H. P. Wilbers (ORCID: https://orcid.org/0000-0003-1149-9268)
- Arifa Ozir‐Fazalalikhan (ORCID: https://orcid.org/0000-0002-0613-8372)
- Bart Everts (ORCID: https://orcid.org/0000-0002-3764-5131)
- Katja Obieglo (ORCID: https://orcid.org/0000-0001-5617-2029)
- Sjoerd Schetters (ORCID: https://orcid.org/0000-0003-2589-4226)
- Maaike R. Scheenstra (ORCID: https://orcid.org/0000-0001-5476-3562)
- Eline van Bloois
Institutions
- Leiden University Medical Center (NL)
- Ghent University Hospital (BE)
- Ghent University (BE)
- Ruhrlandklinik (DE)
- VIB-UGent Center for Inflammation Research (BE)
- The University of Texas Southwestern Medical Center (US)
- Wageningen University & Research (NL)
Publication Details
- Journal
- PLoS Pathogens
- Published
- 2024-08-26
- DOI
- https://doi.org/10.1371/journal.ppat.1012457
- Citations
- 3
- Primary Topic
- Parasites and Host Interactions
- Type
- article
- Field-Weighted Citation Impact
- 1.55
Funders
- ZonMw
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Lung Foundation Netherlands