The formins FMNL1 and mDia1 regulate coiling phagocytosis of Borrelia burgdorferi by primary human macrophages.

摘要: Spirochetes of the Borrelia burgdorferi sensu lato complex are causative agent Lyme borreliosis, a tick-borne infectious disease primarily affecting skin, nervous system, and joints. During infection, macrophages dendritic cells first immune to encounter invading borreliae. Phagocytosis intracellular processing by these is thus decisive for eventual outcome infection. Phagocytic uptake proceeds preferentially through coiling phagocytosis, which characterized actin-rich unilateral pseudopods that capture enwrap spirochetes. Actin-dependent growth necessitates de novo nucleation actin filaments, regulated actin-nucleating factors such as Arp2/3 complex. Here, we demonstrate that, in addition, also actin-regulatory proteins formin family important borreliae primary human macrophages. Using immunofluorescence, live-cell imaging, ratiometric analysis, find specific enrichment formins FMNL1 mDia1 at macrophage contact with Consistently, small interfering RNA (siRNA)-mediated knockdown or leads decreased formation Borrelia-induced internalization Our results suggest phagocytosis process involving several nucleation/regulatory factors. They point specifically novel regulators spirochete cells.