Time‐dependent distinct roles of Toll‐like receptor 4 in a house dust mite‐induced asthma mouse model

• Published in: Scandinavian journal of immunology Vol. 87; no. 3
• Main Authors: Ishii, T., Niikura, Y., Kurata, K., Muroi, M., Tanamoto, K., Nagase, T., Sakaguchi, M., Yamashita, N.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-03-2018
• Subjects: Allergens; Allergies; Asthma; Dust; Eosinophils; experimental animal; House dust; Immune response; Immunoglobulin E; Inflammation; Innate immunity; Intranasal administration; Leukocytes (eosinophilic); Leukocytes (neutrophilic); lipopolysaccharide; Lungs; Mice; Mites; Rodents; TLR4 protein; Toll-like receptors; Lipopolysaccharide; Inflammation; asthma; Experimental animal; Eosinophils
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/sji.12641

House dust mites (HDMs) are a common source of allergens that trigger both allergen‐specific and innate immune responses in humans. Here, we examined the effect of allergen concentration and the involvement of Toll‐like receptor 4 (TLR4) in the process of sensitization to house dust mite allergens in an HDM extract‐induced asthma mouse model.　Intranasal administration of HDM extract induced an immunoglobulin E response and eosinophilic inflammation in a dose‐dependent manner from 2.5 to 30 μg/dose. In TLR4‐knockout mice, the infiltration of eosinophils and neutrophils into the lung was decreased compared with that in wild‐type mice in the early phase of inflammation (total of three doses). However, in the late phase of inflammation (total of seven doses), eosinophil infiltration was significantly greater in TLR4‐knockout mice than in wild‐type mice. This suggests that the roles of TLR4 signaling are different between the early phase and the later phase of HDM allergen‐induced inflammation. Thus, innate immune response through TLR4 regulated the response to HDM allergens, and the regulation was altered during the phase of inflammation.