Surfactant protein D inhibits mite-induced alveolar macrophage and dendritic cell activations through TLR signalling and DC-SIGN expression
Article first published online: 2 NOV 2009
© 2009 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 40, Issue 1, pages 111–122, January 2010
How to Cite
Liu, C.-F., Rivere, M., Huang, H.-J., Puzo, G. and Wang, J.-Y. (2010), Surfactant protein D inhibits mite-induced alveolar macrophage and dendritic cell activations through TLR signalling and DC-SIGN expression. Clinical & Experimental Allergy, 40: 111–122. doi: 10.1111/j.1365-2222.2009.03367.x
- Issue published online: 15 DEC 2009
- Article first published online: 2 NOV 2009
- Submitted 10 April 2009; revised 14 August 2009; accepted 18 August 2009
- alveolar macrophages;
- dendritic cells;
- surfactant protein D;
- Toll-like receptor 4
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.