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
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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.

Metrics

  • 6,470
    Page views
  • 1,220
    Downloads
  • 58
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Categories and tags

Research organism

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. Immunology and Inflammation

    Exploratory mass cytometry analysis reveals immunophenotypes of cancer treatment-related pneumonitis

    Toyoshi Yanagihara, Kentaro Hata ... Isamu Okamoto
    Research Article

    Anticancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of the major opportunistic infections is Pneumocystis jirovecii pneumonia (PCP), which can cause severe respiratory complications and high mortality rates. Cytotoxic drugs and immune-checkpoint inhibitors (ICIs) can induce interstitial lung diseases (ILDs). Nonetheless, the differentiation of these diseases can be difficult, and the pathogenic mechanisms of such diseases are not yet fully understood. To better comprehend the immunophenotypes, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid from patients with PCP, cytotoxic drug-induced ILD (DI-ILD), and ICI-associated ILD (ICI-ILD) using two panels containing 64 markers. In PCP, we observed an expansion of the CD16+ T cell population, with the highest CD16+ T proportion in a fatal case. In ICI-ILD, we found an increase in CD57+ CD8+ T cells expressing immune checkpoints (TIGIT+ LAG3+ TIM-3+ PD-1+), FCRL5+ B cells, and CCR2+ CCR5+ CD14+ monocytes. These findings uncover the diverse immunophenotypes and possible pathomechanisms of cancer treatment-related pneumonitis.