Neutrophils represent key components of the innate immune system with the ability not only to phagocytose and killing invading pathogens, but also to produce a variety of proteins, including cytokines and chemokines, with important consequences on the recruitment and activation of other immune cells, such as monocytes, dendritic cells, T and B cells. For instance, it has been shown that neutrophils can directly interact with, and induce functional maturation of, immature monocyte-derived dendritic cells (moDC). Indeed, upon interaction with neutrophils, moDC up-regulate the expression of costimulatory molecules, such as CD83, CD86 and CD40, and secrete IL-12, thus acquiring the ability to induce proliferation and Th1 polarization of naïve T cells. In order to extend these findings, the present study was designed to address whether human neutrophils interact with peripheral blood-derived dendritic cells and the pathological consequences that such interaction could eventually produce. In human peripheral blood, dendritic cells can be divided in plasmacytoid dendritic cells (pDC) and myeloid dendritic cells (mDC), the latter further divided in three different subsets based on the expression of CD1c, BDCA-3, and CD16. By analyzing different chronic inflammatory pathologies, such as Crohn's disease, psoriasis and Sweet's syndrome, we found that neutrophils co-localize with a subtype of myeloid dendritic cells (mDC) with characteristics resembling the CD16+ subset of mDC. In order to characterize the interaction between the two cell types, autologous neutrophils, highly purified by an in-house built immunonegative selection protocol, and CD16+ DC were isolated from healthy donors and analyzed in a co-culture system under different stimulatory conditions. Here we show that neutrophils modulate different effector functions of CD16+ DC, including their survival and their ability to produce IL-12p70. Besides providing the basis for a better understanding of the cellular interactions that occur in pathological conditions, our results further emphasize the importance of neutrophils in the modulation of the inflammatory response.
Characterization of the cross-talk between human neutrophils and a subset of pro-inflammatory dendritic cells
COSTANTINI, Claudio;CALZETTI, Federica;PERBELLINI, Omar;CASSATELLA, Marco Antonio
2009-01-01
Abstract
Neutrophils represent key components of the innate immune system with the ability not only to phagocytose and killing invading pathogens, but also to produce a variety of proteins, including cytokines and chemokines, with important consequences on the recruitment and activation of other immune cells, such as monocytes, dendritic cells, T and B cells. For instance, it has been shown that neutrophils can directly interact with, and induce functional maturation of, immature monocyte-derived dendritic cells (moDC). Indeed, upon interaction with neutrophils, moDC up-regulate the expression of costimulatory molecules, such as CD83, CD86 and CD40, and secrete IL-12, thus acquiring the ability to induce proliferation and Th1 polarization of naïve T cells. In order to extend these findings, the present study was designed to address whether human neutrophils interact with peripheral blood-derived dendritic cells and the pathological consequences that such interaction could eventually produce. In human peripheral blood, dendritic cells can be divided in plasmacytoid dendritic cells (pDC) and myeloid dendritic cells (mDC), the latter further divided in three different subsets based on the expression of CD1c, BDCA-3, and CD16. By analyzing different chronic inflammatory pathologies, such as Crohn's disease, psoriasis and Sweet's syndrome, we found that neutrophils co-localize with a subtype of myeloid dendritic cells (mDC) with characteristics resembling the CD16+ subset of mDC. In order to characterize the interaction between the two cell types, autologous neutrophils, highly purified by an in-house built immunonegative selection protocol, and CD16+ DC were isolated from healthy donors and analyzed in a co-culture system under different stimulatory conditions. Here we show that neutrophils modulate different effector functions of CD16+ DC, including their survival and their ability to produce IL-12p70. Besides providing the basis for a better understanding of the cellular interactions that occur in pathological conditions, our results further emphasize the importance of neutrophils in the modulation of the inflammatory response.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
