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BMC Immunology
Published in: BMC Immunology 1/2009

Open Access 01-12-2009 | Research article

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

Authors: Anke Leichtle, Michelle Hernandez, Kwang Pak, Nicholas J Webster, Stephen I Wasserman, Allen F Ryan

Published in: BMC Immunology | Issue 1/2009

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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.
Appendix
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Metadata
Title
The Toll-Like receptor adaptor TRIF contributes to otitis media pathogenesis and recovery
Authors
Anke Leichtle
Michelle Hernandez
Kwang Pak
Nicholas J Webster
Stephen I Wasserman
Allen F Ryan
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2009
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/1471-2172-10-45

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