SLE Monocyte Subsets Are Pro-Inflammatory and Display Dysregulated Metabolism in Response to Bacterial Stimuli

Abstract Systemic lupus erythematosus (SLE) is associated with infection susceptibility and altered innate immune function. Monocyte metabolism is linked to appropriate cytokine release and bacterial containment. We investigated cytokine production and metabolic programming in the monocyte population from SLE patients and healthy controls following lipopolysaccharide (LPS) stimulation. SLE monocytes displayed increased IL-10, TNF, and IL-8 production, with impaired IL-1β induction. Metabolic profiling revealed altered substrate use, with increased glucose dependence and reduced fatty acid and amino acid oxidation after LPS stimulation. SLE patients exhibited reduced numbers of classical monocytes, expansion of intermediate monocytes, and dysregulated subset-specific metabolic reprogramming in response to LPS. This descriptive study provides a cornerstone for (i) understanding infection susceptibility in SLE, (ii) subset-resolved immunometabolic profiling as a tool in autoimmunity, and (iii) developing future metabolic-targeted therapeutic strategies Highlights Descriptive mapping shows SLE monocytes are proinflammatory with glucose dependence after LPS Classical and intermediate SLE subsets show divergent baseline metabolic preferences versus healthy SLE subsets display aberrant LPS responses, i.e.. increased glucose and reduced fatty acid oxidation This study provides a cornerstone for subset-resolved immunometabolism in infection susceptibility. Competing Interest Statement The authors have declared no competing interest.