Clements DR, Murphy JP, Sterea A, Kennedy BE, Kim Y, Helson E, Almasi S, Holay N, Konda P, Paulo JA, Sharif T, Lee PW, Weekes MP, Gygi SP, Gujar S. Quantitative Temporal in Vivo Proteomics Deciphers the Transition of Virus-Driven Myeloid Cells into M2 Macrophages.
J Proteome Res 2017;
16:3391-3406. [PMID:
28768414 PMCID:
PMC5648240 DOI:
10.1021/acs.jproteome.7b00425]
[Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
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.
Collapse