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Using Fluorescent Proteins to Visualize and Quantitate Chlamydia Vacuole Growth Dynamics in Living Cells
Published on: October 13, 2015
Extrusions are phagocytosed and promote Chlamydia survival within macrophages
Meghan Zuck1,2, Tisha Ellis1, Anthony Venida2
1Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
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.
Insights
Chlamydia trachomatis uses unique extrusions to exit host cells, enhancing survival and evading immune responses. These extrusions act as "Trojan horses," enabling bacteria to infect macrophages for dissemination and transmission.
Area of Science:
- Microbiology
- Cell Biology
- Immunology
Background:
- Intracellular pathogens utilize specific exit strategies impacting host dissemination and immune evasion.
- Chlamydia trachomatis, an obligate intracellular bacterium, employs both lysis and extrusion for host cell exit.
- The characteristics and advantages of Chlamydia extrusions remain poorly understood.
Purpose of the Study:
- To define the characteristics of Chlamydia trachomatis extrusions.
- To investigate the role of extrusions in bacterial survival and host cell interaction.
- To elucidate the mechanism by which extrusions facilitate Chlamydia dissemination and immune evasion.
Main Methods:
- Characterization of extrusions based on composition and membrane properties.
- Assessment of extracellular survival of Chlamydia within extrusions.
- In vitro phagocytosis assays using bone marrow-derived macrophages and extrusions.
- Analysis of Chlamydia survival and replication within macrophages post-extrusion uptake.
Main Results:
- Extrusions are double-membraned structures, primarily containing Chlamydia elementary bodies and phosphatidylserine on their outer surface.
- Extrusions provide a protective niche, enhancing Chlamydia survival outside the host cell.
- Chlamydial extrusions are phagocytosed by macrophages, shielding bacteria from immune killing and facilitating the release of infectious elementary bodies.
Conclusions:
- Chlamydia trachomatis extrusions are specialized structures facilitating bacterial survival and immune evasion.
- Extrusions act as "Trojan horses," enabling Chlamydia to exploit macrophages for dissemination.
- This mechanism highlights a novel strategy for pathogen spread and potential transmission.
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