TLR3 modulates immunopathology during a Schistosoma mansoni egg-driven Th2 response in the lung
We examined the role of TLR3 in Th2-driven pulmonary granulomatous disease, using wildtype (TLR3(+/+)) and TLR3 gene-deficient (TLR3(-/-)) mice in a well-established model of Schistosoma mansoni egg-induced pulmonary granuloma. The intravenous bolus injection of S. mansoni eggs into S. mansoni-sensitized TLR3(+/+) mice was associated with an increase in TLR3 transcript expression in alveolar macrophages and ex vivo spleen and lung cultures at day 8 after egg injection. Lungs from TLR3(-/-) mice showed an increase in granuloma size, greater collagen deposition around the granuloma, and increased Th2 cytokine and chemokine levels compared with similarly sensitized and challenged TLR3(+/+) mice. Macrophages from TLR3(-/-) mice exhibited an M2 phenotype characterized by increased arginase and CCL2 expression. Significantly greater numbers of CD4(+)CD25(+) T cells were present in the lungs of TLR3(-/-) mice compared with TLR3(+/+) mice at day 8 after egg embolization. Cells derived from granulomatous lung and lung draining lymph nodes of TLR3(-/-) mice released significantly higher levels of IL-17 levels relative to TLR3(+/+) cells. Thus, our data suggest that TLR3 has a major regulatory role during a Th2-driven granulomatous response as its absence enhanced immunopathology.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2008 |
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Erschienen: |
2008 |
Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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Enthalten in: |
European journal of immunology - 38(2008), 12 vom: 11. Dez., Seite 3436-49 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Joshi, Amrita D [VerfasserIn] |
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Links: |
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Themen: |
Cytokines |
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Anmerkungen: |
Date Completed 11.02.2009 Date Revised 20.10.2021 published: Print Citation Status MEDLINE |
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doi: |
10.1002/eji.200838629 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM184496381 |
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520 | |a We examined the role of TLR3 in Th2-driven pulmonary granulomatous disease, using wildtype (TLR3(+/+)) and TLR3 gene-deficient (TLR3(-/-)) mice in a well-established model of Schistosoma mansoni egg-induced pulmonary granuloma. The intravenous bolus injection of S. mansoni eggs into S. mansoni-sensitized TLR3(+/+) mice was associated with an increase in TLR3 transcript expression in alveolar macrophages and ex vivo spleen and lung cultures at day 8 after egg injection. Lungs from TLR3(-/-) mice showed an increase in granuloma size, greater collagen deposition around the granuloma, and increased Th2 cytokine and chemokine levels compared with similarly sensitized and challenged TLR3(+/+) mice. Macrophages from TLR3(-/-) mice exhibited an M2 phenotype characterized by increased arginase and CCL2 expression. Significantly greater numbers of CD4(+)CD25(+) T cells were present in the lungs of TLR3(-/-) mice compared with TLR3(+/+) mice at day 8 after egg embolization. Cells derived from granulomatous lung and lung draining lymph nodes of TLR3(-/-) mice released significantly higher levels of IL-17 levels relative to TLR3(+/+) cells. Thus, our data suggest that TLR3 has a major regulatory role during a Th2-driven granulomatous response as its absence enhanced immunopathology | ||
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