IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to<i>Toxoplasma gondii</i>
Abstract IL-33 is an alarmin required for resistance to the parasiteToxoplasma gondii, but its role in innate resistance to this infection is unclear.T. gondiiinfection promotes increased stromal cell expression of IL-33 and levels of parasite replication correlate with IL-33 release. In response to infection, a subset of innate lymphoid cells (ILC) emerges composed of IL-33R+NK cells and ILC1s. In Rag-/-mice, where NK cells and ILC1 provide an innate mechanism of resistance toT. gondii, the loss of IL-33R reduced ILC responses and increased parasite replication. Furthermore, administration of IL-33 to Rag-/-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 toT. gondii..
Medienart: |
Preprint |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
bioRxiv.org - (2023) vom: 17. Okt. Zur Gesamtaufnahme - year:2023 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Clark, Joseph T. [VerfasserIn] |
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Links: |
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Themen: |
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doi: |
10.1101/2021.01.10.426122 |
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funding: |
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PPN (Katalog-ID): |
XBI019727100 |
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520 | |a Abstract IL-33 is an alarmin required for resistance to the parasiteToxoplasma gondii, but its role in innate resistance to this infection is unclear.T. gondiiinfection promotes increased stromal cell expression of IL-33 and levels of parasite replication correlate with IL-33 release. In response to infection, a subset of innate lymphoid cells (ILC) emerges composed of IL-33R+NK cells and ILC1s. In Rag-/-mice, where NK cells and ILC1 provide an innate mechanism of resistance toT. gondii, the loss of IL-33R reduced ILC responses and increased parasite replication. Furthermore, administration of IL-33 to Rag-/-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 toT. gondii. | ||
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