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About the Authors:
Felipe H. Santiago-Tirado
Affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
ORCID http://orcid.org/0000-0002-6453-4904
Tamara L. Doering
* E-mail: [email protected]
Affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
ORCID http://orcid.org/0000-0002-5179-7393Citation: Santiago-Tirado FH, Doering TL (2017) False friends: Phagocytes as Trojan horses in microbial brain infections. PLoS Pathog 13(12): e1006680. https://doi.org/10.1371/journal.ppat.1006680
Editor: Donald C. Sheppard, McGill University, CANADA
Published: December 14, 2017
Copyright: © 2017 Santiago-Tirado, Doering. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: Work cited in this review from the Doering lab was supported by the National Institute of Allergy and Infectious Diseases (https://www.niaid.nih.gov) grants AI114549, AI102882, and AI078795 to TLD; NIH T32 AI007172 to FHS; and a Burroughs Wellcome Fund (https://www.bwfund.org) Postdoctoral Enrichment Award to FHS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Humans are constantly exposed to pathogenic microbes. The first line of cellular host defense is composed of “professional” phagocytes, cells that efficiently recognize pathogens, internalize them, and then marshal an array of antimicrobial mechanisms to destroy them. Nevertheless, successful pathogens evade or survive such attack. A particularly subversive strategy is to manipulate normal phagocyte behaviors to benefit the microbe, sometimes even turning the phagocyte from a threat to a safe haven. In this environment, the microbes can multiply while protected from immune surveillance, and in some cases, even travel to the most protected host site, the brain. This gives rise to the Trojan horse analogy: like the wooden horse that carried hidden enemies through the gates into the walled city of Troy, phagocytes carry intracellular microbes through the blood-brain barrier (BBB) into the central nervous system (CNS).
Immune cells in the brain
Traditionally, the brain has been considered an immune-privileged site because it lacks the normal robust inflammatory responses to antigenic challenges. However, it does have an active immune surveillance system [1] that involves the extravasation of leukocytes,...