Role of MyD88 in adenovirus keratitis

Xiaohong Zhou, Mirja Ramke, Ashish V. Chintakuntlawar, Jeong Yoon Lee, Jaya Rajaiya, James Chodosh

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Pattern recognition receptors (PRRs) are critical to the early detection and innate immune responses to pathogens. In particular, the toll-like receptor (TLR) system and its associated adaptor proteins have essential roles in early host responses to infection. Epidemic keratoconjunctivitis, caused by the human adenovirus, is a severe ocular surface infection associated with corneal inflammation (stromal keratitis). We previously showed that adenovirus capsid was a key molecular pattern in adenovirus keratitis, with viral DNA having a lesser role. We have now investigated the role of the adaptor molecule MyD88 in a mouse model of adenovirus keratitis in which there is no viral replication. In MyD88 -/- mice infected with human adenovirus type 37, clinical keratitis was markedly reduced, along with infiltration of CD45 + cells, and expression of inflammatory cytokines. Reduction of inflammatory cytokines was also observed in infected primary human corneal fibroblasts pretreated with a MyD88 inhibitory peptide. Keratitis similar to wild type mice was observed in TLR2, TLR9 and IL-1R knockout mice, but was reduced in TLR2/9 double knockout mice, consistent with synergy of TLR2 and TLR9 in the response to adenovirus infection. MyD88 co-immunoprecipitated with Src kinase in mice corneas and in human corneal fibroblasts infected with adenovirus, and MyD88 inhibitory peptide reduced Src phosphorylation, linking MyD88 activation to inflammatory gene expression through a signaling cascade previously shown to be directed by Src. Our findings reveal a critical role for the PRRs TLR2 and 9, and their adaptor protein MyD88, in corneal inflammation upon adenovirus infection.

Original languageEnglish (US)
Pages (from-to)108-116
Number of pages9
JournalImmunology and Cell Biology
Volume95
Issue number1
DOIs
StatePublished - Jan 1 2017

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Zhou, X., Ramke, M., Chintakuntlawar, A. V., Lee, J. Y., Rajaiya, J., & Chodosh, J. (2017). Role of MyD88 in adenovirus keratitis. Immunology and Cell Biology, 95(1), 108-116. https://doi.org/10.1038/icb.2016.73