Mammalian cells internalize bacteriophages and use them as a resource to enhance cellular growth and survival

by Marion C. Bichet, Jack Adderley, Laura Avellaneda-Franco, Isabelle Magnin-Bougma, Natasha Torriero-Smith, Linden J. Gearing, Celine Deffrasnes, Cassandra David, Genevieve Pepin, Michael P. Gantier, Ruby CY Lin, Ruzeen Patwa, Gregory W. Moseley, Christian Doerig, Jeremy J. Barr There is a growing appreciation that the direct interaction between bacteriophages and the mammalian host can facilitate diverse and unexplored symbioses. Yet the impact these bacteriophages may have on mammalian cellular and immunological processes is poorly understood. Here, we applied highly purified phage T4, free from bacterial by-products and endotoxins to mammalian cells and analyzed the cellular responses using luciferase reporter and antibody microarray assays. Phage preparations were applied in vitro to either A549 lung epithelial cells, MDCK-I kidney cells, or primary mouse bone marrow derived macrophages with the phage-free supernatant serving as a comparative control. Highly purified T4 phages were rapidly internalized by mammalian cells and accumulated within macropinosomes but did not activate the inflammatory DNA response TLR9 or cGAS-STING pathways. Following 8 hours of incubation with T4 phage, whole cell lysates were analyzed via antibody microarray that detected expression and phosphorylation levels of human signaling proteins. T4 phage application led to the activation of AKT-dependent pathways, resulting in an increase in cell metabolism, survival, and actin reorganization, the...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research