The tempo and mode of gene regulatory programs during bacterial infection

Gal Avital, Felicia Kuperwaser, Andrew W. Pountain, Keenan A. Lacey, Erin E. Zwack, Magdalena Podkowik, Bo Shopsin, Victor J. Torres, Itai Yanai

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Innate immune recognition of bacterial pathogens is a key determinant of the ensuing systemic response, and host or pathogen heterogeneity in this early interaction can impact the course of infection. To gain insight into host response heterogeneity, we investigate macrophage inflammatory dynamics using primary human macrophages infected with Group B Streptococcus. Transcriptomic analysis reveals discrete cellular states within responding macrophages, one of which consists of four sub-states, reflecting inflammatory activation. Infection with six additional bacterial species—Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Yersinia pseudotuberculosis, Shigella flexneri, and Salmonella enterica—recapitulates these states, though at different frequencies. We show that modulating the duration of infection and the presence of a toxin impacts inflammatory trajectory dynamics. We provide evidence for this trajectory in infected macrophages in an in vivo model of Staphylococcus aureus infection. Our cell-state analysis defines a framework for understanding inflammatory activation dynamics in response to bacterial infection.

Original languageEnglish
Article number111477
JournalCell Reports
Volume41
Issue number2
DOIs
StatePublished - 11 Oct 2022
Externally publishedYes

Keywords

  • CP: Molecular biology
  • host-pathogen interactions
  • infection trajectory
  • macrophage response
  • single-cell RNA-seq

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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