IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii
- University of Pennsylvania, United States
- Kangwon National University, Republic of Korea
- University Hospital of Basel and University of Basel, Switzerland
- AstraZeneca, United States
Abstract
IL-33 is an alarmin required for resistance to the parasite Toxoplasma gondii, but its role in innate resistance to this organism is unclear. Infection with T. gondii promotes increased stromal cell expression of IL-33 and levels of parasite replication correlate with release of IL-33 in affected tissues. In response to infection, a subset of innate lymphoid cells (ILC) emerges composed of IL-33R+ NK cells and ILC1s. In Rag1-/- mice, where NK cells and ILC1 production of IFN-g mediates innate resistance to T. gondii, the loss of the IL-33R resulted in reduced ILC responses and increased parasite replication. Furthermore, administration of IL-33 to Rag1-/- mice resulted in a marked decrease in parasite burden, increased production of IFN-g and the recruitment and expansion of inflammatory monocytes associated with parasite control. These protective effects of exogenous IL-33 were dependent on endogenous IL-12p40 and the ability of IL-33 to enhance ILC production of IFN-g. These results highlight that IL-33 synergizes with IL-12 to promote ILC-mediated resistance to T. gondii.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Christopher A Hunter
Funding
National Institute of Allergy and Infectious Diseases (5R01AI125563-05)
- Christopher A Hunter
National Institute of Allergy and Infectious Diseases (5T32AI00753223)
- Christopher A Hunter
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Gabrielle T Belz, The University of Queensland, Australia
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#805045) of the University of Pennsylvania
Version history
- Received: December 9, 2020
- Accepted: April 29, 2021
- Accepted Manuscript published: April 30, 2021 (version 1)
- Version of Record published: May 14, 2021 (version 2)
Copyright
© 2021, Clark et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii
eLife 10:e65614.
https://doi.org/10.7554/eLife.65614
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