The Toll-Like receptor adaptor TRIF contributes to otitis media pathogenesis and recovery

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  • Leichtle, Anke
    • Other Affiliation: Department of Surgery/Otolaryngology, University of California, San Diego, 9500 Gilman Avenue, La Jolla, California 92093, USA; Department of Otolaryngology, University of Lubeck, Ratzeburger Allee 160, Lubeck 23538, Germany
  • Hernandez, Michelle
    • Affiliation: School of Medicine, Division of Rheumatology, Allergy and Immunology, Department of Medicine
    • Other Affiliation: Department of Medicine/Rheumatology, Allergy and Immunology, University of California, San Diego, 9500 Gilman Avenue, La Jolla, California 92093, USA
  • Pak, Kwang
    • Other Affiliation: Department of Surgery/Otolaryngology, University of California, San Diego, 9500 Gilman Avenue, La Jolla, California 92093, USA
  • Webster, Nicholas J
    • Other Affiliation: Department of Medicine/Endocrinology, University of California, San Diego, 9500 Gilman Avenue, La Jolla, California 92093, USA
  • Wasserman, Stephen I
    • Other Affiliation: Department of Medicine/Rheumatology, Allergy and Immunology, University of California, San Diego, 9500 Gilman Avenue, La Jolla, California 92093, USA
  • Ryan, Allen F
    • Other Affiliation: Department of Surgery/Otolaryngology, University of California, San Diego, 9500 Gilman Avenue, La Jolla, California 92093, USA
Abstract
  • Abstract Background Toll-like receptor (TLR) signalling is crucial for innate immune responses to infection. The involvement of TLRs in otitis media (OM), the most prevalent childhood disease in developed countries, has been implicated by studies in middle ear cell lines, by association studies of TLR-related gene polymorphisms, and by altered OM in mice bearing mutations in TLR genes. Activated TLRs signal via two alternative intracellular signaling molecules with differing effects; MyD88 (Myeloid differentiation primary response gene 88) inducing primarily interleukin expression and TRIF (Tir-domain-containing adaptor inducing interferon β) mediating type I interferon (IFN) expression. We tested the hypothesis that TRIF and type I IFN signaling play a role in OM, using a murine model of OM induced by non-typeable Haemophilus influenzae (NTHi). The ME inflammatory response to NTHi was examined in wild-type (WT) and TRIF-/- mice by qPCR, gene microarray, histopathology and bacterial culture. Results Expression of TRIF mRNA was only modesty enhanced during OM, but both type I IFN signalling genes and type I IFN-inducible genes were significantly up-regulated in WT mice. TRIF-deficient mice showed reduced but more persistent mucosal hyperplasia and less leukocyte infiltration into the ME in response to NTHi infection than did WT animals. Viable bacteria could be cultured from MEs of TRIF-/- mice for much longer in the course of disease than was the case for middle ears of WT mice. Conclusion Our results demonstrate that activation of TRIF/type I IFN responses is important in both the pathogenesis and resolution of NTHi-induced OM.
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  • Article
Rights statement
  • In Copyright
Rights holder
  • Anke Leichtle et al.; licensee BioMed Central Ltd.
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Journal title
  • BMC Immunology
Journal volume
  • 10
Journal issue
  • 1
Page start
  • 45
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1471-2172
Bibliographic citation
  • BMC Immunology. 2009 Aug 05;10(1):45
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • August 23, 2012

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file details 1471-2172-10-45.pdf 2019-05-07 Public Download
file details Type I Interferon-Induced Genes (IFNα_β >IFNγ, ref. 35) Microarray Data. The data represent the medians, ranges and significance levels of the microarray values presented in Figure 3C. 2019-05-07 Public Download
file details 1471-2172-10-45.xml 2019-05-07 Public Download
file details TRIF Signaling Genes Microarray Data. The data represent the medians, ranges and significance levels of the microarray values presented in Figure 3A. 2019-05-07 Public Download
file details Type I Interferon Genes Microarray Data. The data represent the medians, ranges and significance levels of the microarray values presented in Figure 3B. 2019-05-07 Public Download