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J Proteome Res. 2017 Sep 1;16(9):3391-3406. doi: 10.1021/acs.jproteome.7b00425. Epub 2017 Aug 23.

Quantitative Temporal in Vivo Proteomics Deciphers the Transition of Virus-Driven Myeloid Cells into M2 Macrophages.

Author information

1
Faculty of Medicine, University of Toronto , Toronto, Ontario M5S 1A8, Canada.
2
Department of Cell Biology, Harvard Medical School , Boston, Massachusetts 02115, United States.
3
Cambridge Institute for Medical Research, University of Cambridge , Cambridge CB2 0XY, United Kingdom.
4
Centre for Innovative and Collaborative Health Systems Research, IWK Health Centre , Halifax, Nova Scotia B3K 6R8, Canada.

Abstract

Myeloid cells play a central role in the context of viral eradication, yet precisely how these cells differentiate throughout the course of acute infections is poorly understood. In this study, we have developed a novel quantitative temporal in vivo proteomics (QTiPs) platform to capture proteomic signatures of temporally transitioning virus-driven myeloid cells directly in situ, thus taking into consideration host-virus interactions throughout the course of an infection. QTiPs, in combination with phenotypic, functional, and metabolic analyses, elucidated a pivotal role for inflammatory CD11b+, Ly6G-, Ly6Chigh-low cells in antiviral immune response and viral clearance. Most importantly, the time-resolved QTiPs data set showed the transition of CD11b+, Ly6G-, Ly6Chigh-low cells into M2-like macrophages, which displayed increased antigen-presentation capacities and bioenergetic demands late in infection. We elucidated the pivotal role of myeloid cells in virus clearance and show how these cells phenotypically, functionally, and metabolically undergo a timely transition from inflammatory to M2-like macrophages in vivo. With respect to the growing appreciation for in vivo examination of viral-host interactions and for the role of myeloid cells, this study elucidates the use of quantitative proteomics to reveal the role and response of distinct immune cell populations throughout the course of virus infection.

KEYWORDS:

M2-like macrophages; infection; myeloid cells; proteomics

PMID:
28768414
PMCID:
PMC5648240
DOI:
10.1021/acs.jproteome.7b00425
[Indexed for MEDLINE]
Free PMC Article

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