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Cell DOI:10.1016/j.cell.2015.08.027

Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses.

Publication TypeJournal Article
Year of Publication2015
AuthorsAvraham, R, Haseley, N, Brown, D, Penaranda, C, Jijon, HB, Trombetta, JJ, Satija, R, Shalek, AK, Xavier, RJ, Regev, A, Hung, DT
JournalCell
Volume162
Issue6
Pages1309-21
Date Published2015 Sep 10
ISSN1097-4172
KeywordsAnimals, Host-Pathogen Interactions, Interferon Type I, Lipopolysaccharides, Macrophages, Mice, Mice, Inbred C57BL, Salmonella Infections, Salmonella typhimurium, Specific Pathogen-Free Organisms
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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0092-8674(15)01041-7
DOI10.1016/j.cell.2015.08.027
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/26343579?dopt=Abstract

Alternate JournalCell
PubMed ID26343579
PubMed Central IDPMC4578813
Grant ListU19 AI109725 / AI / NIAID NIH HHS / United States
DK043351 / DK / NIDDK NIH HHS / United States
F32 HD075541 / HD / NICHD NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
P50 HG006193) / HG / NHGRI NIH HHS / United States
T32 HG002295 / HG / NHGRI NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
F32 HD075541-02 / HD / NICHD NIH HHS / United States
U19AI109725 / AI / NIAID NIH HHS / United States
HG002295 / HG / NHGRI NIH HHS / United States