1. Immunology and Inflammation
  2. Microbiology and Infectious Disease

Trogocytosis-associated cell to cell spread of intracellular bacterial pathogens

  1. Shaun Steele
  2. Lauren Radlinski
  3. Sharon Taft-Benz
  4. Brunton Jason
  5. Thomas H Kawula  Is a corresponding author
  1. University of North Carolina at Chapel Hill, United States
https://doi.org/10.7554/eLife.10625
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  1. Shaun Steele
  2. Lauren Radlinski
  3. Sharon Taft-Benz
  4. Brunton Jason
  5. Thomas H Kawula
(2016)
Trogocytosis-associated cell to cell spread of intracellular bacterial pathogens
eLife 5:e10625.
https://doi.org/10.7554/eLife.10625
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Abstract

Macrophages are myeloid-derived phagocytic cells and one of the first immune cell types to respond to microbial infections. However, a number of bacterial pathogens are resistant to the antimicrobial activities of macrophages and can grow within these cells. Macrophages have other immune surveillance roles including the acquisition of cytosolic components from multiple types of cells. We hypothesized that intracellular pathogens that can replicate within macrophages could also exploit cytosolic transfer to facilitate bacterial spread. We found that viable Francisella tularensis, as well as Salmonella enterica bacteria transferred from infected cells to uninfected macrophages along with other cytosolic material through a transient, contact dependent mechanism. Bacterial transfer occurred when the host cells exchanged plasma membrane proteins and cytosol via a trogocytosis related process leaving both donor and recipient cells intact and viable. Trogocytosis was strongly associated with infection in mice, suggesting that direct bacterial transfer occurs by this process in vivo.

Article and author information

Author details

  1. Shaun Steele

    University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Lauren Radlinski

    University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Sharon Taft-Benz

    University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Brunton Jason

    University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Thomas H Kawula

    University of North Carolina at Chapel Hill, Chapel Hill, United States
    For correspondence
    kawula@med.unc.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Denise Monack, Stanford, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#13-213.0) of the University of North Carolina.

Version history

  1. Received: August 5, 2015
  2. Accepted: January 22, 2016
  3. Accepted Manuscript published: January 23, 2016 (version 1)
  4. Version of Record published: February 26, 2016 (version 2)

Copyright

© 2016, Steele et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Shaun Steele
  2. Lauren Radlinski
  3. Sharon Taft-Benz
  4. Brunton Jason
  5. Thomas H Kawula
(2016)
Trogocytosis-associated cell to cell spread of intracellular bacterial pathogens
eLife 5:e10625.
https://doi.org/10.7554/eLife.10625

Share this article

https://doi.org/10.7554/eLife.10625

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Further reading

    1. Microbiology and Infectious Disease

    Francisella tularensis enters a double membraned compartment following cell-cell transfer

    Shaun P Steele, Zach Chamberlain ... Thomas H Kawula
    Research Advance Updated

    Previously, we found that phagocytic cells ingest bacteria directly from the cytosol of infected cells without killing the initially infected cell (Steele et al., 2016). Here, we explored the events immediately following bacterial transfer. Francisella tularensis bacteria acquired from infected cells were found within double-membrane vesicles partially composed from the donor cell plasma membrane. As with phagosomal escape, the F. tularensis Type VI Secretion System (T6SS) was required for vacuole escape. We constructed a T6SS inducible strain and established conditions where this strain is trapped in vacuoles of cells infected through bacterial transfer. Using this strain we identified bacterial transfer events in the lungs of infected mice, demonstrating that this process occurs in infected animals. These data and electron microscopy analysis of the transfer event revealed that macrophages acquire cytoplasm and membrane components of other cells through a process that is distinct from, but related to phagocytosis.

    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Intracellular Bacteria: Catch me if you can

    Emilie Bourdonnay, Thomas Henry
    Insight

    Direct contact between host cells allows some bacteria to spread within the body without being attacked by the immune system.

    1. Cell Biology
    2. Immunology and Inflammation

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    Cytokine polyfunctionality is a well-established concept in immune cells, especially T cells, and their ability to concurrently produce multiple cytokines has been associated with better immunological disease control and subsequent effectiveness during infection and disease. To date, only little is known about the secretion dynamics of those cells, masked by the widespread deployment of mainly time-integrated endpoint measurement techniques that do not easily differentiate between concurrent and sequential secretion. Here, we employed a single-cell microfluidic platform capable of resolving the secretion dynamics of individual PBMCs. To study the dynamics of poly-cytokine secretion, as well as the dynamics of concurrent and sequential polyfunctionality, we analyzed the response at different time points after ex vivo activation. First, we observed the simultaneous secretion of cytokines over the measurement time for most stimulants in a subpopulation of cells only. Second, polyfunctionality generally decreased with prolonged stimulation times and revealed no correlation with the concentration of secreted cytokines in response to stimulation. However, we observed a general trend towards higher cytokine secretion in polyfunctional cells, with their secretion dynamics being distinctly different from mono-cytokine-secreting cells. This study provided insights into the distinct secretion behavior of heterogenous cell populations after stimulation with well-described agents and such a system could provide a better understanding of various immune dynamics in therapy and disease.