title: Extrusions are phagocytosed and promote Chlamydia survival within macrophages.
abstract: The precise strategies that intracellular pathogens use to exit host cells have a direct impact on their ability to disseminate within a host, transmit to new hosts, and engage or avoid immune responses. The obligate intracellular bacterium Chlamydia trachomatis exits the host cell by two distinct exit strategies, lysis and extrusion. The defining characteristics of extrusions, and advantages gained by Chlamydia within this unique double-membrane structure, are not well understood. Here, we define extrusions as being largely devoid of host organelles, comprised mostly of Chlamydia elementary bodies, and containing phosphatidylserine on the outer surface of the extrusion membrane. Extrusions also served as transient, intracellular-like niches for enhanced Chlamydia survival outside the host cell. In addition to enhanced extracellular survival, we report the key discovery that chlamydial extrusions are phagocytosed by primary bone marrow-derived macrophages, after which they provide a protective microenvironment for Chlamydia. Extrusion-derived Chlamydia staved off macrophage-based killing and culminated in the release of infectious elementary bodies from the macrophage. Based on these findings, we propose a model in which C. trachomatis extrusions serve as "trojan horses" for bacteria, by exploiting macrophages as vehicles for dissemination, immune evasion, and potentially transmission.
authors.affiliation: Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.|Division of Infectious Diseases and Immunity, School of Public Health, University of California, Berkeley, California, USA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Zuck
authors.affiliation: Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
authors.forename: Tisha
authors.initials: T
authors.lastname: Ellis
authors.affiliation: Division of Infectious Diseases and Immunity, School of Public Health, University of California, Berkeley, California, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Venida
authors.affiliation: Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
authors.forename: Kevin
authors.identifier: 0000-0002-2967-3079
authors.initials: K
authors.lastname: Hybiske
mesh_terms: D000818:Animals; D002690:Chlamydia Infections / Q000276:immunology / Q000382:microbiology*; D002692:Chlamydia trachomatis / Q000502:physiology* / Q000648:ultrastructure; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D050296:Microbial Viability; D010587:Phagocytosis
keywords: Chlamydia; exit; extrusion; macrophage; phagocytosis