Development of Exhausted Memory Monocytes and Underlying Mechanisms.

ABSTRACT: Pathogenic inflammation and immuno-suppression are cardinal features of exhausted monocytes increasingly recognized in septic patients and murine models of sepsis. However, underlying mechanisms responsible for the generation of exhausted monocytes have not been addressed. In this report, we examined the generation of exhausted primary murine monocytes through prolonged and repetitive challenges with high dose bacterial endotoxin lipopolysaccharide (LPS). We demonstrated that repetitive LPS challenges skew monocytes into the classically exhausted Ly6C^hi population, and deplete the homeostatic non-classical Ly6C^lo population, reminiscent of monocyte exhaustion in septic patients. scRNAseq analyses confirmed the expansion of Ly6C^hi monocyte cluster, with elev

SUBMITTER: Pradhan K 

PROVIDER: S-EPMC8583871 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature