| Title: |
Quantitative temporal in vivo proteomics (QTiPs) deciphers the transition of virus-driven myeloid cells into M2 macrophages |
| Authors: |
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 |
| Publisher Information: |
American Chemical Society; //doi.org/10.1021/acs.jproteome.7b00425; Journal of Proteome Research |
| Publication Year: |
2017 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
infection; M2-like macrophages; myeloid cells; proteomics |
| Description: |
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‾, Ly6C^high-low cells in antiviral immune response and viral clearance. Most importantly, the time-resolved QTiPs data set showed the transition of CD11b⁺, Ly6G‾, Ly6C^high-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. ; This work was supported by grants from the Canadian Institutes of Health Research (CIHR) and Terry Fox Research Institute (TFRI) to S.G. and P.W.L. Authors D.R.C., Y.K., and T.S. are supported by the CIHR. J.P.M. and B.E.K. are supported through the Cancer Research Training Program (CRTP) of BHCRI. D.R.C. was supported previously by CRTP from BHCRI and the Nova Scotia Health Research Foundation (NSHRF). Nova Scotia Graduate Scholarships fund both N.H. and P.K. Work by J.A.P. was funded in part by NIH/NIDDK grant K01 DK098285. M.P.W. was supported by a Wellcome Trust Senior Fellowship (108070/Z/15/Z). We ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/267452 |
| DOI: |
10.17863/CAM.12361 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/267452; https://doi.org/10.17863/CAM.12361 |
| Rights: |
Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.96829A60 |
| Database: |
BASE |