The NHANES study identified several pollens and cat dander as the most common allergens that induce allergic sensitization and allergic diseases. We recently reported that ragweed pollen extract (RWPE) requires TLR4 to stimulate CXCL-mediated innate neutrophilic inflammation that facilitates allergic sensitization and airway inflammation. Myeloid differentiation protein-2 (MD2) is a TLR4 coreceptor, but its role in pollen and cat dander-induced innate and allergic inflammation has not been critically evaluated. To elucidate the role of MD2 in inducing pollen and cat dander-induced innate and allergic airway inflammation.
TCMNull (TLR4Null, CD14Null, MD2Null), TLR4Hi, TCMHicells and human bronchial epithelial cells with siRNA-induced downregulation of MD2 were stimulated with RWPE, other pollen allergic extracts, or cat dander extract (CDE), and activation of NF-κB and/or secretion of the NF-κB-dependent CXCL8 were quantified. Wild type (WT) mice or mice with siRNA knockdown of lung MD2 were challenged intranasally with RWPE or CDE, and innate and allergic inflammation were quantified.
RWPE stimulated MD2-dependent NF-κB activation and CXCL secretion. Likewise, Bermuda, rye, timothy, pigweed, Russian thistle, cottonwood, walnut and CDE stimulated MD2-dependent CXCL secretion. RWPE and CDE challenge induced MD2-dependent, CD14-independent innate neutrophil recruitment. RWPE induced MD2-dependent allergic sensitization and airway inflammation.
MD2 plays an important role in induction of allergic sensitization to cat dander and common pollens relevant to human allergic diseases.