Neutrophils mediate immune modulation of dendritic cells through glycosylation-dependent interactions between Mac-1 and DC-SIGN.
Neutrophils are key players of the innate immune system that provide a first line of defense against invading pathogens. However, it is unknown whether neutrophils can interact with dendritic cells (DCs) to modulate adaptive immune responses. We demonstrate that neutrophils strongly cluster with immature DCs and that activated, not resting, neutrophils induce maturation of DCs that enables these DCs to trigger strong T cell proliferation and T helper type 1 polarization of T cells. This neutrophil-DC interaction is driven by the binding of the DC-specific, C-type lectin DC-SIGN to the beta(2)-integrin Mac-1. Strikingly, DC-SIGN only interacts with Mac-1 from neutrophils, but not from other leukocytes, mainly because of specific Lewis(x) carbohydrates that are present on the alpha(M) chain of Mac-1 from neutrophils. Furthermore, we show that besides the formation of cellular contact, the tumor necrosis factor-alpha produced by activated neutrophils is essential for inducing DC maturation. Our data demonstrate that DC-SIGN and Mac-1 define a molecular pathway to establish cellular adhesion between DCs and neutrophils, thereby providing a novel cellular link between innate and adaptive immunity.
van Gisbergen
Klaas P J M
KP
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, 1081 BT Amsterdam, Netherlands.
Sanchez-Hernandez
Marta
M
Geijtenbeek
Teunis B H
TB
van Kooyk
Yvette
Y
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D020014:K562 Cells; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin