The proteomic landscape of blood monocytes in community-acquired pneumonia

INTRODUCTION: Monocytes play a pivotal role in the regulation of inflammation and pathogen clearance during infection. Knowledge of the human monocyte proteome during infection is limited. We present a comprehensive proteome profile of blood monocytes from patients with community-acquired pneumonia (CAP), one of the most common infectious diseases, and controls without infection. METHODS: Monocytes were purified from blood of patients with CAP within 16 h of admission to a general hospital ward and from controls matched for sex, age and comorbidities. Monocyte proteins were measured using liquid chromatography/mass spectrometry. The transcriptome was analysed in the same samples by RNA sequencing. Monocytes were stimulated with lipopolysaccharide for 24 h, after which cytokines were measured in the supernatant. RESULTS: We analysed the monocyte proteome of 34 CAP patients and 23 controls. Out of 7315 annotated proteins, 1340 (18.3%) were differentially abundant between groups. Functional enrichment analyses revealed a marked downregulation of mitochondrial respiration processes in patient monocytes; pathways pertaining to cell cycle, cytokine signalling and cell death were upregulated in patient monocytes. Monocyte mRNA levels correlated poorly with the abundance of corresponding proteins and associated functional pathways, raising caution regarding interpretation of functionality estimates based on transcriptome analyses. Differential expression of monocyte proteins had functional and clinical implications as indicated by associations with cytokine production capacity, disease severity and time to clinical stability. CONCLUSION: This study provides a publicly available monocyte protein atlas that can serve as a resource for future research on monocyte functions during infection.