IL-18BP mediates the balance between protective and pathological immune responses to Toxoplasma gondii
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
Interleukin-18 (IL-18) promotes natural killer (NK) and T cell production of interferon (IFN)-γ, a key factor in resistance to Toxoplasma gondii, but previous work has shown a limited role for endogenous IL-18 in control of this parasite. Although infection with T. gondii results in release of IL-18, the production of IFN-γ induces high levels of the IL-18 binding protein (IL-18BP). Antagonism of IL-18BP with a "decoy-to-the-decoy" (D2D) IL-18 construct that does not signal but rather binds IL-18BP results in enhanced innate lymphoid cell (ILC) and T cell responses and improved parasite control. In addition, the use of IL-18 resistant to IL-18BP ("decoy-resistant" IL-18 [DR-18]) is more effective than exogenous IL-18 at promoting innate resistance to infection. DR-18 enhances CD4+ T cell production of IFN-γ but results in CD4+ T cell-mediated pathology. Thus, endogenous IL-18BP restrains aberrant immune pathology, and this study highlights strategies that can be used to tune this regulatory pathway for optimal anti-pathogen responses.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Cell reports - 42(2023), 3 vom: 28. März, Seite 112147 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Clark, Joseph T [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.04.2023 Date Revised 09.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2023.112147 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a IL-18BP mediates the balance between protective and pathological immune responses to Toxoplasma gondii |
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| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Interleukin-18 (IL-18) promotes natural killer (NK) and T cell production of interferon (IFN)-γ, a key factor in resistance to Toxoplasma gondii, but previous work has shown a limited role for endogenous IL-18 in control of this parasite. Although infection with T. gondii results in release of IL-18, the production of IFN-γ induces high levels of the IL-18 binding protein (IL-18BP). Antagonism of IL-18BP with a "decoy-to-the-decoy" (D2D) IL-18 construct that does not signal but rather binds IL-18BP results in enhanced innate lymphoid cell (ILC) and T cell responses and improved parasite control. In addition, the use of IL-18 resistant to IL-18BP ("decoy-resistant" IL-18 [DR-18]) is more effective than exogenous IL-18 at promoting innate resistance to infection. DR-18 enhances CD4+ T cell production of IFN-γ but results in CD4+ T cell-mediated pathology. Thus, endogenous IL-18BP restrains aberrant immune pathology, and this study highlights strategies that can be used to tune this regulatory pathway for optimal anti-pathogen responses | ||
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| 700 | 1 | |a Aldridge, Daniel L |e verfasserin |4 aut | |
| 700 | 1 | |a Shallberg, Lindsey A |e verfasserin |4 aut | |
| 700 | 1 | |a Eberhard, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Lanzar, Zachary |e verfasserin |4 aut | |
| 700 | 1 | |a Wasche, Devon |e verfasserin |4 aut | |
| 700 | 1 | |a Huck, John D |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Ring, Aaron M |e verfasserin |4 aut | |
| 700 | 1 | |a Hunter, Christopher A |e verfasserin |4 aut | |
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