Published ahead of print on February 26, 2009, doi:10.1164/rccm.200806-974OC © 2009 American Thoracic Society doi: 10.1164/rccm.200806-974OC
Toll/IL-1 Signaling Is Critical for House Dust Mite–specific Th1 and Th2 Responses1 Centre for Asthma and Respiratory Diseases, School of Biomedical Sciences, University of Newcastle, Newcastle; 2 Monash Institute of Medical Research, Monash University, Clayton; 3 Gene Targeting Group, John Curtin School of Medical Research, Australian National University, Canberra, Australia; and 4 Stem Cell Unit, Department of Anatomy, College of Medicine, and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia Correspondence and requests for reprints should be addressed to P. Foster, Ph.D., and S. Phipps, Ph.D., Centre for Asthma and Respiratory Diseases, David Maddison Clinical Sciences Building, Watt Street, Newcastle, NSW, 2300 Australia. E-mail: paul.foster{at}newcastle.edu.au and simon.phipps{at}newcastle.edu.au 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- 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.
Key Words: asthma • innate immunity • eosinophil • neutrophil
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B 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. 
