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. Genetics and Genomics
    2. Immunology and Inflammation

    Transposable elements regulate thymus development and function

    Jean-David Larouche, Céline M Laumont ... Claude Perreault
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    Transposable elements (TEs) are repetitive sequences representing ~45% of the human and mouse genomes and are highly expressed by medullary thymic epithelial cells (mTECs). In this study, we investigated the role of TEs on T-cell development in the thymus. We performed multiomic analyses of TEs in human and mouse thymic cells to elucidate their role in T-cell development. We report that TE expression in the human thymus is high and shows extensive age- and cell lineage-related variations. TE expression correlates with multiple transcription factors in all cell types of the human thymus. Two cell types express particularly broad TE repertoires: mTECs and plasmacytoid dendritic cells (pDCs). In mTECs, transcriptomic data suggest that TEs interact with transcription factors essential for mTEC development and function (e.g., PAX1 and REL), and immunopeptidomic data showed that TEs generate MHC-I-associated peptides implicated in thymocyte education. Notably, AIRE, FEZF2, and CHD4 regulate small yet non-redundant sets of TEs in murine mTECs. Human thymic pDCs homogenously express large numbers of TEs that likely form dsRNA, which can activate innate immune receptors, potentially explaining why thymic pDCs constitutively secrete IFN ɑ/β. This study highlights the diversity of interactions between TEs and the adaptive immune system. TEs are genetic parasites, and the two thymic cell types most affected by TEs (mTEcs and pDCs) are essential to establishing central T-cell tolerance. Therefore, we propose that orchestrating TE expression in thymic cells is critical to prevent autoimmunity in vertebrates.