Dataset Information

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

ABSTRACT:

Background

We have shown previously that murine gammaherpesvirus 68 (?HV68) infection exacerbates established pulmonary fibrosis. Because Toll-like receptor (TLR)-9 may be important in controlling the immune response to ?HV68 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)-? after viral infection. Balb/c fibroblasts infected with ?HV68 in vitro produced more IFN-? 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.

SUBMITTER: Luckhardt TR

PROVIDER: S-EPMC3163187 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Luckhardt Tracy R TR Coomes Stephanie M SM Trujillo Glenda G Stoolman Joshua S JS Vannella Kevin M KM Bhan Urvashi U Wilke Carol A CA Moore Thomas A TA Toews Galen B GB Hogaboam Cory C Moore Bethany B BB

Fibrogenesis & tissue repair 20110802

<h4>Background</h4>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.<h4>Results</h4>We found that in ...[more]

PMID: 21810214

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