Surfactant protein D inhibits mite-induced alveolar macrophage and dendritic cell activations through TLR signalling and DC-SIGN expression

• Published in: Clinical and experimental allergy 2010-01, Vol.40 (1), p.111-122
• Main Authors: Liu, C-F, Rivere, M., Huang, H-J, Puzo, G., Wang, J-Y
• Format: Article
• Language: English
• Subjects: allergens; Allergens - immunology; alveolar macrophages; Animals; Antigens, Dermatophagoides - immunology; asthma; CD14; Cell Adhesion Molecules - biosynthesis; Cell Adhesion Molecules - metabolism; Cells, Cultured; DC-SIGN; dendritic cells; Dendritic Cells - immunology; Dermatophagoides pteronyssinus; Dermatophagoides pteronyssinus - immunology; Down-Regulation - drug effects; Humans; Kinases; Lectins, C-Type - biosynthesis; Lectins, C-Type - metabolism; Macrophages, Alveolar - immunology; Mice; Mice, Inbred BALB C; Nitric Oxide - biosynthesis; Proteins; Pulmonary Surfactant-Associated Protein D - metabolism; Pulmonary Surfactant-Associated Protein D - pharmacology; Receptors, Cell Surface - biosynthesis; Receptors, Cell Surface - metabolism; Recombinant Proteins - pharmacology; Signal Transduction; surfactant protein D; Surfactants; Toll-like receptor 4; Toll-Like Receptors - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2009.03367.x

Summary Background Surfactant protein D (SP‐D), a secreted pattern recognition molecule associated with pulmonary innate immunity, has been shown to mediate the clearance of pathogens in multiple ways. However, how SP‐D interacts with alveolar macrophages (AMs) and dendritic cells (DCs) during allergen exposure remains unclear. Objective This study was performed to characterize the immunomodulatory effects of SP‐D on mite allergen (Dermatophagoides pteronyssinus, Der p)‐induced inflammatory signalling in AMs and DCs. Methods Murine AM, alveolar macrophage cell line derived from BALB/c mice (MH‐S cells), and human monocyte‐derived dendritic cells (MDDC) were used as model systems. The production of nitric oxide (NO) and TNF‐α, expression of surface Toll‐like receptors (TLRs), and expression of the C‐type lectin receptor known as dendritic cell (DC)‐specific ICAM‐grabbing non‐integrin (DC‐SIGN) were measured as a function of pretreatment with SP‐D and subsequent exposure to Der p. Der p‐dependent cellular activations that were modified by SP‐D in these model systems were then identified. Results Pretreatment of MH‐S cells with SP‐D reduced Der p‐dependent production of NO, TNF‐α, and the downstream activations of IL‐1 receptor‐associated kinase, mitogen activated protein kinase (MAPK) kinase, and nuclear factor‐κB. SP‐D interacted with CD14 such that CD14 binding to Der p was inhibited and Der p‐induced signalling via TLRs was blocked. DC‐SIGN expression was suppressed by Der p in MH‐S and MDDC; this down‐regulation of DC‐SIGN expression was prevented by pretreatment with SP‐D. Conclusions These results indicated that the inhibition of Der p‐induced activation of MH‐S and MDDC by SP‐D is mediated through suppression of the CD14/TLR signalling pathway and maintenance of DC‐SIGN expression, which may protect allergen‐induced airway inflammation. Cite this as: C‐F Liu, M. Rivere, H‐J Huang, G. Puzo and J‐Y Wang, Clinical & Experimental Allergy, 2010 (40) 111–122.