rOIT induced desensitization to egg and thus improved the QOL of guardians; however, the participants experienced frequent allergic reactions due to the treatment.
Purpose of review
To discuss the presence and role of neutrophils in asthma and allergic diseases, and outline importance of pollen and cat dander-induced innate neutrophil recruitment in induction of allergic sensitization and allergic inflammation.
Recent findings
Uncontrolled asthma is associated with elevated numbers of neutrophils, and levels of neutrophil-attracting chemokine IL-8 and IL-17 in BAL fluids. These parameters negatively correlate with lung function. Pollen allergens and cat dander recruit neutrophils to the airways in a TLR4, MD2 and CXCR2-dependent manner. Repeated recruitment of activated neutrophils by these allergens facilitates allergic sensitization and airway inflammation. Inhibition of neutrophil recruitment with CXCR2 inhibitor, disruption of TLR4, or siRNA against MD2 also inhibits allergic inflammation. The molecular mechanisms by which neutrophils shift the inflammatory response of the airways to inhaled allergens to an allergic phenotype is an area of active research.
Summary
Recent studies have revealed that neutrophil recruitment is important in development of allergic sensitization and inflammation. Inhibition of neutrophils recruitment may be strategy to control allergic inflammation.
Background
The NHANES study identified several pollens and cat dander among 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.
Objective
To elucidate the role of MD2 in inducing pollen and cat dander-induced innate and allergic airway inflammation.
Methods
TCMNull (TLR4Null, CD14Null, MD2Null), TLR4Hi, TCMHi cells 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.
Results
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.
Conclusions
MD2 plays an important role in induction of allergic sensitization to cat dander and common pollens relevant to human allergic diseases.
Duration of breastfeeding, season of birth, pet ownership, household income, and the number of siblings were associated with the prevalence of childhood eczema in a nationwide web survey.
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