The control of cell behaviour through material geometry is appealing as it avoids the requirement for complex chemical surface modifications. Significant advances in new technologies have been made to the development of polymeric biomaterials with controlled geometry and physico-chemical properties. Solution blow spinning technique has the advantage of ease of use allowing the production of nano or microfibres and the direct fibre deposition on any surface in situ. Yet, in spite of these advantages, very little is known about the influence of such fibres on biological functions such as immune response and cell migration. In this work, we engineered polymeric fibres composed of either pure poly(lactic acid) (PLA) or blends of PLA and polyethylene glycol (PEG) by solution blow spinning and determined their impact on dendritic cells, highly specialised cells essential for immunity and tolerance. We also determined the influence of fibres on cell adhesion and motility. Cells readily interacted with fibres resulting in an intimate contact characterised by accumulation of actin filaments and focal adhesion components at sites of cell-fibre interactions. Moreover, cells were guided along the fibres and actin and focal adhesion components showed a highly dynamic behaviour at cell-fibre interface. Remarkably, fibres did not elicit any substantial increase of activation markers and inflammatory cytokines in dendritic cells, which remained in their immature (inactive) state. Taken together, these findings will be useful for developing new biomaterials for applications in tissue engineering and regenerative medicine.