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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61443/1/3436_ftp.pd