TLR9-induced interferon β is associated with protection from gammaherpesvirus-induced exacerbation of lung fibrosis

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Abstract

Background: We have shown previously that murine gammaherpesvirus 68 (γHV68) infection exacerbates established pulmonary fibrosis. Because Toll-like receptor (TLR)-9 may be important in controlling the immune response to γHV68 infection, we examined how TLR-9 signaling effects exacerbation of fibrosis in response to viral infection, using models of bleomycin- and fluorescein isothiocyanate-induced pulmonary fibrosis in wild-type (Balb/c) and TLR-9-/- mice.Results: We found that in the absence of TLR-9 signaling, there was a significant increase in collagen deposition following viral exacerbation of fibrosis. This was not associated with increased viral load in TLR-9-/- mice or with major alterations in T helper (Th)1 and Th2 cytokines. We examined alveolar epithelial-cell apoptosis in both strains, but this could not explain the altered fibrotic outcomes. As expected, TLR-9-/- mice had a defect in the production of interferon (IFN)-β after viral infection. Balb/c fibroblasts infected with γHV68 in vitro produced more IFN-β than did infected TLR-9-/- fibroblasts. Accordingly, in vitro infection of Balb/c fibroblasts resulted in reduced proliferation rates whereas infection of TLR-9-/- fibroblasts did not. Finally, therapeutic administration of CpG oligodeoxynucleotides ameliorated bleomycin-induced fibrosis in wild-type mice.Conclusions: These results show a protective role for TLR-9 signaling in murine models of lung fibrosis, and highlight differences in the biology of TLR-9 between mice and humans. © 2011 Luckhardt et al; licensee BioMed Central Ltd.

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Luckhardt, T. R., Coomes, S. M., Trujillo, G., Stoolman, J. S., Vannella, K. M., Bhan, U., … Moore, B. B. (2011). TLR9-induced interferon β is associated with protection from gammaherpesvirus-induced exacerbation of lung fibrosis. Fibrogenesis and Tissue Repair, 4(1). https://doi.org/10.1186/1755-1536-4-18

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