Cat Dander Extract Requires Myd88 to Induce Innate Neutrophil Recruitment, and Allergic Sensitization and Allergic Airway Inflammation.
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Toshiko Itazawa, MD, PhD, Koa Hosoki, MD, PhD, Istvan Boldogh, PhD, Sanjiv Sur, MD
Rationale: We have reported that intranasal challenge with ragweed pollen extract (RWPE) induces TLR4-dependent recruitment of neutrophils to the airways, and this neutrophil recruitment is critical for facilitating allergic sensitization and allergic airway inflammation. Cat dander is a major indoor antigen that induces an early wave of neutrophil recruitment in asthmatic subjects. In this study, we examined the molecular mechanisms of cat dander-induced neutrophil recruitment and allergic inflammation.

Methods: In the innate model, WT, Tlr4KO, Tlr2KO and Myd88KO mice were intranasally challenged once with cat dander extract (CDE).  BALF levels of neutrophils were quantified 16 h later. In the allergic model, WT and Myd88KO mice were sensitized with 5 intranasal doses of CDE and challenged with CDE to elucidate allergic airway inflammation.  

Results: In the innate model, CDE challenge in WT mice increased recruitment of neutrophils to the airways. This recruitment was reduced by 50% in both Tlr4 and Tlr2KO mice, and abrogated in Myd88KO mice. In the allergic model, repeated-challenge with CDE in WT mice induced allergic sensitization and allergic airway inflammation characterized by increase of total cells and eosinophils in BALF, elevation of the levels of IL-5, IL-13, IL-33, and TSLP in BALF, stimulation of mucin in airway epithelial cells, and increase of total IgE and CDE specific IgE in serum. However, all parameters were abolished in Myd88KO mice.

Conclusions: These results indicate that Myd88 is essential for mediating CDE-induced innate neutrophil recruitment, and stimulating allergic sensitization and allergic airway inflammation.