HDM-induced Allergic Airway Inflammation Model
Objective: Assessment of allergic airway inflammation and immune responses induced by house dust mite allergen inhalation in mice, with focus on TLR4 expression on airway structural cells and dendritic cell activation
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Protocol Steps
HDM allergen inhalation exposure
Mice were exposed to house dust mite allergen via inhalation to induce allergic airway inflammation
Note: This is the primary sensitization/challenge method for the allergic airway inflammation model
View evidence from paper
“inhalation of house dust mite (HDM) allergen and endotoxin”
Assessment of airway structural cell TLR4 expression
Evaluation of TLR4 expression on radioresistant lung structural cells using irradiated chimeric mice to determine requirement for allergic response
Note: Used irradiated chimeric mice to distinguish TLR4 function on structural cells versus hematopoietic cells
View evidence from paper
“Using irradiated chimeric mice, we demonstrate that TLR4 expression on radioresistant lung structural cells is required and sufficient”
Measurement of innate proallergic cytokine production
Assessment of thymic stromal lymphopoietin, granulocyte-macrophage colony stimulating factor, interleukin-25 and IL-33 production following TLR4 triggering on structural cells
Note: These cytokines are produced as a result of TLR4 triggering on airway structural cells
View evidence from paper
“TLR4 triggering on structural cells caused production of the innate proallergic cytokines thymic stromal lymphopoietin, granulocyte-macrophage colony stimulating factor, interleukin-25 and IL-33”
Evaluation of dendritic cell activation
Assessment of dendritic cell activation in the lung following TLR4 signaling on structural cells
Note: DC activation is required for priming of effector T helper responses to HDM
View evidence from paper
“TLR4 expression on radioresistant lung structural cells is required and sufficient for DC activation in the lung”
Assessment of T helper cell priming
Evaluation of effector T helper responses to HDM allergen
Note: T helper priming is dependent on DC activation and structural cell TLR4 signaling
View evidence from paper
“for priming of effector T helper responses to HDM”
Measurement of allergic airway inflammation
Assessment of HDM-driven allergic airway inflammation in mice with and without TLR4 on structural cells
Note: Absence of TLR4 on structural cells abolishes HDM-driven allergic airway inflammation
View evidence from paper
“The absence of TLR4 on structural cells, but not on hematopoietic cells, abolished HDM driven allergic airway inflammation”
Assessment of bronchial hyperreactivity
Measurement of bronchial hyperreactivity as a key feature of asthma following TLR4 antagonist treatment
Note: TLR4 antagonist inhalation suppressed bronchial hyperreactivity
View evidence from paper
“inhalation of a TLR4 antagonist to target exposed epithelial cells suppressed the salient features of asthma including bronchial hyperreactivity”