TLR3 modulates immunopathology during a Schistosoma mansoni egg-driven Th2 response in the lung
✍ Scribed by Amrita D. Joshi; Matthew A. Schaller; Nicholas W. Lukacs; Steven L. Kunkel; Cory M. Hogaboam
- Book ID
- 102824647
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 535 KB
- Volume
- 38
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
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.