Neutrophils mediated immune modulation of dendritic cells through glycosylation-dependent interactions between Mac-1 and DC-SIGN

Van Gisbergen et al. 2005. J. Exp. Med. 201:1281-1292.

Speaker: 林士超                          Date: 2005/10/26

Commentator: 謝奇璋 醫師             Time: 15:10-16:00

Room: 601

Abstract:

Neutrophils have been thought the first line against invasive pathogens in immune system. Recently, it has become clear that the regulatory function of neutrophils to signal to other immune cells¹. However, the interaction between neutrophils and dendritic cells is still unclear. The Dendritic Cell Immunobiology Group of Free University in Netherlands has established the molecular mechanism about how neutrophils interact with dendritic cells. They found this cell-cell adhesion is mediated by mac-1 and DC-SIGN which expressed on neutrophils and dendritic cells, respectively. DC-SIGN, discovered originally by the same authors, plays an important role for cellular adhesion between dendritic cells and T cells or endothelial cells². Furthermore, the authors also identified a carbohydrate moiety, Lewis^x, within Mac-1 is a determinant recognized by DC-SIGN. This data was re-confirmed by means of anti-DCSIGN monoclonal antibody, AZN-D1.On the other hand, they also use α1-3,4-fucosidase to remove Lewis^x to gain the same result. Previously studies have shown Lewis^x also expressed on tropical parasite (Schistosoma monsoni) egg antigens (SEAs) can interact with DC-SIGN to activate dendritic cells and elicit T cell responses³. Similarly, the interaction between Lewis^x of Mac-1 and DC-SIGN can stimulate neutrophils to secret TNF-a and activate dendritic cells so that regulate T cell responses indirectly. In a word, the authors have demonstrated a novel cellular adhesion within innate immunity and provide a new link between adaptive and innate immunity.

Referances:

1.      Witko-Sarsat et al. 2000. Neutrophils: molecules, functions and pathophysiological aspects. Lab. Invest. 80:617-653.

2.      Geijtenbeek, T. B. H. et al. 2000. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that support primary immune responses. Cell. 100:575-585.

3.      van Die, I. et al. 2003. The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x. Glycobiology. 13:471-478.