Faculty, Staff and Student Publications
Publication Date
10-11-2022
Journal
Cell Reports
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.
Keywords
CP, Molecular biology, host-pathogen interactions, infection trajectory, macrophage response, single-cell RNA-seq
DOI
10.1016/j.celrep.2022.111477
PMID
36223751
PMCID
PMC9741813
PubMedCentral® Posted Date
December 2022
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes