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Datasets  >  signalling dataset  >  Cross-talk between human mD...

Cross-talk between human mDC and pDC

signalling dataset

We have obtained data on a possible cooperation between myeloid and plasmacytoid DCs in response to different microbial stimuli and a characterization of the mechanisms of this cooperation. For this, we have studied co-culture of mDCs and pDCs in response to CpGs, LPS and bacterial particles.

Taking advantage on the fact that human myeloid and plasmacitoid DC show a selective response to LPS and CpG respectively, we have previously identified a cross-talk between two type of cells. Indeed it was observed that LPS-stimulated mDCs are able to induce up-regulation of co-stimulatory molecules on co-cultured pDCs. Similarly, CpG-stimulated pDCs activate co-cultured mDCs. Activation of the co-cultured population was restricted to up-regulation of co-stimulatory molecules and was partially cell contact-dependent. We have now investigated if co-operation between mDCs and pDCs is able to facilitate the induction of adaptive immunity in conditions of low stimulation, which can be encountered in the very early phase of a pathogen infection or in the presence of very low amounts of pathogen. In particular we analyzed if the synergy between mDCs and pDCs stimulated by their respective selective stimulus is important for increasing their ability at inducing T cell activation. Indeed we established that the mDC/pDC cross-talk has a functional effect on T cell activation. In fact the mDC/pDC cooperation event is able to significantly increase the ability of these cells to drive the proliferation and IFN? production by alloreactive T cells. In addition, we discovered that pDCs are not able to respond to whole fixed or live bacteria and consequently, these cells are incapable of phagocytosing bacterial particles. These finding strongly suggest that pDCs is a cellular population that plays a very specialized antiviral function, although, through a cross-talk with mDC, it can also be indirectly recruited during a bacterial infection, synergizing in the induction of an adaptive immune response.

We will investigate the molecular mechanism through which a mDC/pDC cross-activation occurs. In particular, since the mDC/pDC cross-talk process that we identified is dependent on cell-contact events, we will try to identify the molecule/s responsible for cross-activation between mDCs and pDCs.






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