Single-Cell Analysis of CX3CR1+ Cells Reveals a Pathogenic Role for BIRC5+ Myeloid Proliferating Cells Driven by Staphylococcus aureus Leukotoxins
Journal
Journal of immunology
Journal Volume
211
Journal Issue
5
Pages
836-843
Date Issued
2023-09-01
Author(s)
Loredan, Denis G
Devlin, Joseph C
Lacey, Keenan A
Howard, Nina
Chen, Ze
Zwack, Erin E
Ruggles, Kelly V
Khanna, Kamal M
Torres, Victor J
Loke, P'ng
Abstract
Our previous studies identified a population of stem cell-like proliferating myeloid cells within inflamed tissues that could serve as a reservoir for tissue macrophages to adopt different activation states depending on the microenvironment. By lineage-tracing cells derived from CX3CR1+ precursors in mice during infection and profiling by single-cell RNA sequencing, in this study, we identify a cluster of BIRC5+ myeloid cells that expanded in the liver during chronic infection with either the parasite Schistosoma mansoni or the bacterial pathogen Staphylococcus aureus. In the absence of tissue-damaging toxins, S. aureus infection does not elicit these BIRC5+ cells. Moreover, deletion of BIRC5 from CX3CR1-expressing cells results in improved survival during S. aureus infection. Hence the combination of single-cell RNA sequencing and genetic fate-mapping CX3CR1+ cells revealed a toxin-dependent pathogenic role for BIRC5 in myeloid cells during S. aureus infection.
SDGs
Publisher
NLM (Medline)
Type
journal article