Recycling endosomal membranes contribute to Toxoplasma gondii parasitophorous vacuole formation in mast cells (45.4)

Abstract

Abstract For the obligate intracellular parasite, Toxoplasma gondii, elucidating its initial interactions with host cells and their parasitophorous vacuole membrane (PVM) is important for better understanding T. gondii infection. In many cell types, recycling endosomal (RE) trafficking often contributes to plasma membrane remodeling during processes such as phagocytosis. Previously, we characterized RE trafficking in RBL-2H3 mast cells and demonstrated IgE/antigen-stimulated outward trafficking of FITC-cholera toxin B (CTxB) bound to GM1 on RE membranes. When these cells are infected with virulent Type I strain tachyzoites, we find that invading parasites have an accumulation of FITC-CTxB on the PVM at early times after infection. This response is substantially enhanced when FITC-CTxB labels the RE pool in addition to the plasma membrane, providing evidence that RE membranes contribute to the nascent PVM. Consistent with earlier studies, IgE bound to its receptor at the plasma membrane shows no detectable accumulation at the PVM during this early stage (first hour) of infection. Under these conditions, antigen-stimulated degranulation is substantially inhibited, suggesting that parasitic infection interferes with normal signaling responses in these cells. Our ongoing research aims to further investigate the possible link between the PVM and RE trafficking and the potential immunomodulatory effects of T. gondii on infected mast cell signaling.