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 scRNA-seq, here we identify a cluster of BIRC5+ myeloid cells that expanded in the liver during either chronic infection with 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 scRNA-Seq and genetic fate mapping CX3CR1+ cells revealed a toxin dependent pathogenic role for BIRC5 in myeloid cells during S. aureus infection.
Competing Interest Statement
P.L. is a federal employee. V.J.T. has consulted for Janssen Research & Development, LLC and has received honoraria from Genentech and Medimmune. V.J.T. is also an inventor on patents and patent applications filed by New York University, which are currently under commercial license to Janssen Biotech Inc. Janssen Biotech Inc. provides research funding and other payments associated with a licensing agreement.
Footnotes
Grant Support: This research was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), AI099394 (VJT), AI105129 (VJT), AI133977 (VJT), AI143861 (KMK), AI143861-S1 (KMK)