TLR3 modulates immunopathology during a Schistosoma mansoni egg-driven Th2 response in the lung

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 TLR31/1 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. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.