IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii
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 t...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
eLife Sciences Publications Ltd
2021-04-01
|
Series: | eLife |
Subjects: | |
Online Access: | https://elifesciences.org/articles/65614 |
id |
doaj-52e090cac47b4fec91345db4426581e2 |
---|---|
record_format |
Article |
spelling |
doaj-52e090cac47b4fec91345db4426581e22021-05-14T15:00:49ZengeLife Sciences Publications LtdeLife2050-084X2021-04-011010.7554/eLife.65614IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondiiJoseph T Clark0https://orcid.org/0000-0001-7764-6000David A Christian1Jodi A Gullicksrud2Joseph A Perry3Jeongho Park4Maxime Jacquet5James C Tarrant6Enrico Radaelli7Jonathan Silver8Christopher A Hunter9https://orcid.org/0000-0003-3092-1428Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, United StatesDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, United StatesDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, United StatesDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, United StatesDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, United States; Kangwon National University College of Veterinary Medicine and Institute of Veterinary Science, Chuncheon, Republic of KoreaDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, United States; Liver Immunology, Department of Biomedicine, University Hospital of Basel and University of Basel, Basel, SwitzerlandDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, United StatesDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, United StatesDepartment of Respiratory Inflammation and Autoimmunity, AstraZeneca, Gaithersburg, United StatesDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, United StatesIL-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-γ mediate 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-γ, 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-γ. These results highlight that IL-33 synergizes with IL-12 to promote ILC-mediated resistance to T. gondii.https://elifesciences.org/articles/65614Toxoplasma gondiiIL-33IL-1 familyinnate lymphoid cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Joseph T Clark David A Christian Jodi A Gullicksrud Joseph A Perry Jeongho Park Maxime Jacquet James C Tarrant Enrico Radaelli Jonathan Silver Christopher A Hunter |
spellingShingle |
Joseph T Clark David A Christian Jodi A Gullicksrud Joseph A Perry Jeongho Park Maxime Jacquet James C Tarrant Enrico Radaelli Jonathan Silver Christopher A Hunter IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii eLife Toxoplasma gondii IL-33 IL-1 family innate lymphoid cells |
author_facet |
Joseph T Clark David A Christian Jodi A Gullicksrud Joseph A Perry Jeongho Park Maxime Jacquet James C Tarrant Enrico Radaelli Jonathan Silver Christopher A Hunter |
author_sort |
Joseph T Clark |
title |
IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii |
title_short |
IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii |
title_full |
IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii |
title_fullStr |
IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii |
title_full_unstemmed |
IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii |
title_sort |
il-33 promotes innate lymphoid cell-dependent ifn-γ production required for innate immunity to toxoplasma gondii |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2021-04-01 |
description |
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-γ mediate 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-γ, 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-γ. These results highlight that IL-33 synergizes with IL-12 to promote ILC-mediated resistance to T. gondii. |
topic |
Toxoplasma gondii IL-33 IL-1 family innate lymphoid cells |
url |
https://elifesciences.org/articles/65614 |
work_keys_str_mv |
AT josephtclark il33promotesinnatelymphoidcelldependentifngproductionrequiredforinnateimmunitytotoxoplasmagondii AT davidachristian il33promotesinnatelymphoidcelldependentifngproductionrequiredforinnateimmunitytotoxoplasmagondii AT jodiagullicksrud il33promotesinnatelymphoidcelldependentifngproductionrequiredforinnateimmunitytotoxoplasmagondii AT josephaperry il33promotesinnatelymphoidcelldependentifngproductionrequiredforinnateimmunitytotoxoplasmagondii AT jeonghopark il33promotesinnatelymphoidcelldependentifngproductionrequiredforinnateimmunitytotoxoplasmagondii AT maximejacquet il33promotesinnatelymphoidcelldependentifngproductionrequiredforinnateimmunitytotoxoplasmagondii AT jamesctarrant il33promotesinnatelymphoidcelldependentifngproductionrequiredforinnateimmunitytotoxoplasmagondii AT enricoradaelli il33promotesinnatelymphoidcelldependentifngproductionrequiredforinnateimmunitytotoxoplasmagondii AT jonathansilver il33promotesinnatelymphoidcelldependentifngproductionrequiredforinnateimmunitytotoxoplasmagondii AT christopherahunter il33promotesinnatelymphoidcelldependentifngproductionrequiredforinnateimmunitytotoxoplasmagondii |
_version_ |
1721441059554197504 |