Trogocytosis-associated cell to cell spread of intracellular bacterial pathogens

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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.

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Shaun Steele

University of North Carolina at Chapel Hill, Chapel Hill, United States

Competing interests
The authors declare that no competing interests exist.
Lauren Radlinski

University of North Carolina at Chapel Hill, Chapel Hill, United States

Competing interests
The authors declare that no competing interests exist.
Sharon Taft-Benz

University of North Carolina at Chapel Hill, Chapel Hill, United States

Competing interests
The authors declare that no competing interests exist.
Brunton Jason

University of North Carolina at Chapel Hill, Chapel Hill, United States

Competing interests
The authors declare that no competing interests exist.
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.

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.

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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.