Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses
Name
Pathogen cell.pdf
Size
1.44 MB
Format
Adobe PDF
Checksum (MD5)
5265276726ff8f944f4f408079b9cd0b
Author(s)
Avraham, Roi
Brown, Douglas
Penaranda, Cristina
Jijon, Humberto B.
Trombetta, John J.
Satija, Rahul
Xavier, Ramnik J.
Hung, Deborah T.
Haseley, Nathan Scott
Shalek, Alexander K
Date Issued
September 2015
Journal
Cell
Publisher
Elsevier
Citation
Avraham, Roi, Nathan Haseley, Douglas Brown, Cristina Penaranda, Humberto B. Jijon, John J. Trombetta, Rahul Satija, Alex K. Shalek, Ramnik J. Xavier, Aviv Regev, and Deborah T. Hung. “Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses.” Cell 162, no. 6 (September 2015): 1309-1321.
Version
Author's final manuscript
Abstract
Encounters between immune cells and invading bacteria ultimately determine the course of infection. These interactions are usually measured in populations of cells, masking cell-to-cell variation that may be important for infection outcome. To characterize the gene expression variation that underlies distinct infection outcomes and monitor infection phenotypes, we developed an experimental system that combines single-cell RNA-seq with fluorescent markers. Probing the responses of individual macrophages to invading Salmonella, we find that variation between individual infected host cells is determined by the heterogeneous activity of bacterial factors in individual infecting bacteria. We illustrate how variable PhoPQ activity in the population of invading bacteria drives variable host type I IFN responses by modifying LPS in a subset of bacteria. This work demonstrates a causative link between host and bacterial variability, with cell-to-cell variation between different bacteria being sufficient to drive radically different host immune responses. This co-variation has implications for host-pathogen dynamics in vivo.
MIT Department
Institute for Medical Engineering and Science
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
Ragon Institute of MGH, MIT and Harvard
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2015.08.027
