title: Surfactant protein D inhibits mite-induced alveolar macrophage and dendritic cell activations through TLR signalling and DC-SIGN expression.
abstract: 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-alpha, 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-alpha, and the downstream activations of IL-1 receptor-associated kinase, mitogen activated protein kinase (MAPK) kinase, and nuclear factor-kappaB. 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.
authors.affiliation: Department of Pediatrics, Division of Clinical Immunology and Allergy, Institute of Basic Medical Sciences, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
authors.forename: C-F
authors.initials: CF
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Rivere
authors.forename: H-J
authors.initials: HJ
authors.lastname: Huang
authors.forename: G
authors.initials: G
authors.lastname: Puzo
authors.forename: J-Y
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D040002:Dermatophagoides pteronyssinus / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D009569:Nitric Oxide; D037663:Pulmonary Surfactant-Associated Protein D; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin