Dectin-1 Plays an Important Role in House Dust Mite–Induced Allergic Airway Inflammation through the Activation of CD11b+ Dendritic Cells

Abstract

It is well known that sensitization against fungi is closely associated with severity of asthma. Dectin-1 (gene symbol Clec7a), a C-type lectin receptor, recognizes the fungal cell wall component β-glucan, as well as some component(s) in house dust mite (HDM) extract. However, the roles of Dectin-1 in HDM-induced allergic airway inflammation remain unclear. In this study, we used Dectin-1-deficient (Clec7a) mice to examine whether Dectin-1 is involved in HDM-induced allergic airway inflammation. We found that HDM-induced eosinophil and neutrophil recruitment into the airways was significantly attenuated in Clec7a mice compared with that in wild-type mice. In addition, HDM-induced IL-5, IL-13, and IL-17 production from mediastinum lymph node cells was reduced in HDM-sensitized Clec7a mice. Dectin-1 was expressed on CD11b dendritic cells (DCs), an essential DC subset for the development of allergic inflammation, but not on CD103 DCs, plasmacytoid DCs, or lung epithelial cells. Transcriptome analysis revealed that the expression of chemokine/chemokine receptors, including CCR7, which is indispensable for DC migration to draining lymph nodes, was decreased in Clec7a DCs. In accordance with these results, the number of HDM-labeled CD11b DCs in mediastinum lymph nodes was significantly reduced in Clec7a mice compared with wild-type mice. Taken together, these results suggest that Dectin-1 expressed on CD11b DCs senses some molecule(s) in HDM extract and plays a critical role in the induction of HDM-induced allergic airway inflammation by inducing the expression of chemokine/chemokine receptors in DCs.

Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

“…Our data are in contrast to a report showing a proallergic role for dectin-1 in response to HDM (11). However, the study used vendor-bought, unrelated C57BL/6 as controls for comparison with Clec7a −/− mice, and not littermate controls, which may be a considerable confounder as previously reported (12–14).…”

Allergic airway inflammation: key players beyond the Th2 cell pathway

“…In addition, C-type lectin receptors, Dectin-1 and Dectin-2, which recognize fungal cell wall components β-glucan and α-mannan, respectively, enhance IL-23 production from DCs in response to unknown components in house dust mite (HDM) allergens and promote Th17 cell differentiation. [44][45][46][47] Consistently, a large number of Th17 cells and steroid insensitivity are observed in mice sensitized by antigens together with β-glucan, 46 suggesting that signals through C-type lectin receptors induce Th17 cell differentiation.…”

“…Regarding the mechanism underlying Th17 cell differentiation in asthma models, it has been shown that serum amyloid A enhances Th17 cell responses in the lung through IL‐1 production, suggesting that inflammasome‐activating molecules are capable of inducing Th17 cell differentiation. In addition, C‐type lectin receptors, Dectin‐1 and Dectin‐2, which recognize fungal cell wall components β‐glucan and α‐mannan, respectively, enhance IL‐23 production from DCs in response to unknown components in house dust mite (HDM) allergens and promote Th17 cell differentiation . Consistently, a large number of Th17 cells and steroid insensitivity are observed in mice sensitized by antigens together with β‐glucan, suggesting that signals through C‐type lectin receptors induce Th17 cell differentiation.…”

Advanced Role of Neutrophils in Common Respiratory Diseases

“…Similar to that, Siew et al discovered that CSE (cigarette smoke extract), IL-17, and aeroallergens could act on human tracheal epithelial cells and further increase IL-6 and IL-8 production [45]. CD11b + DCs could sense some molecules in HDM extract and play a key role in the induction of HDM-induced allergic airway inflammation by inducing the expression of chemokine or chemokine receptors in DCs by expressing dectin-1 [42]. …”

“…Microbial components, which contain LPS and β -glucan, could synergistically cause neutrophilic asthma mediated by TLR-4 and dectin-1 [41], whose deficiency could significantly attenuate the recruitment of neutrophils induced by house dust mite (HDM) into airways [42]. Blood neutrophils from allergic asthma also show the chemotactic and phagocytic activities towards LPS and asthmatic serum [43].…”