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Am J Respir Crit Care Med. 2009 May 15;179(10):883-93. doi: 10.1164/rccm.200806-974OC. Epub 2009 Feb 26.

Toll/IL-1 signaling is critical for house dust mite-specific helper T cell type 2 and type 17 [corrected] responses.

Author information

  • 1Centre for Asthma and Respiratory Diseases, School of Biomedical Sciences, University of Newcastle, NSW, 2300 Australia. simon.phipps@newcastle.edu.au

Erratum in

  • Am J Respir Crit Care Med. 2009 Nov 15;180(10):1032.

Abstract

RATIONALE:

One of the immunopathological features of allergic inflammation is the infiltration of helper T type 2 (Th2) cells to the site of disease. Activation of innate pattern recognition receptors such as Toll-like receptors (TLRs) plays a critical role in helper T type 1 cell differentiation, yet their contribution to the generation of Th2 responses to clinically relevant aeroallergens remains poorly defined.

OBJECTIVES:

To determine the requirement for TLR2, TLR4, and the Toll/IL-1 receptor domain adaptor protein MyD88 in a murine model of allergic asthma.

METHODS:

Wild-type and factor-deficient ((-/-)) mice were sensitized intranasally to the common allergen house dust mite (HDM) and challenged 2 weeks later on four consecutive days. Measurements of allergic airway inflammation, T-cell cytokine production, and airway hyperreactivity were performed 24 hours later.

MEASUREMENTS AND MAIN RESULTS:

Mice deficient in MyD88 were protected from the cardinal features of allergic asthma, including granulocytic inflammation, Th2 cytokine production and airway hyperreactivity. Although HDM activated NF-kappaB in TLR2- or TLR4-expressing HEK cells, only in TLR4(-/-) mice was the magnitude of allergic airway inflammation and hyperreactivity attenuated. The diminished Th2 response present in MyD88(-/-) and TLR4(-/-) mice was associated with fewer OX40 ligand-expressing myeloid dendritic cells in the draining lymph nodes during allergic sensitization. Finally, HDM-specific IL-17 production and airway neutrophilia were attenuated in MyD88(-/-) but not TLR4(-/-) mice.

CONCLUSIONS:

Together, these data suggest that Th2- and Th17-mediated inflammation generated on inhalational HDM exposure is differentially regulated by the presence of microbial products and the activation of distinct MyD88-dependent pattern recognition receptors.

PMID:
19246719
[PubMed - indexed for MEDLINE]
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