Differences in circulating levels of non-classical monocytes and associated caspase 1 activation during Staphylococcus aureus and Escherichia coli bacteremia

Bloodstream infections (BSI) caused by Escherichia coli and Staphylococcus aureus are frequent and are associated with substantial mortality rate. The host immune response major determinant of the clinical outcomes during BSI. Here, we investigated the innate immune response, by characterizing peripheral blood myeloid cell subsets and caspase-1 activation as a surrogate marker of inflammasome activation in patients with E. coli or S. aureus bacteremia. We prospectively enrolled patients with monomicrobial bacteremia and analyzed peripheral blood samples by flow cytometry. We observed distinct alterations in myeloid cell composition and caspase-1 activation associated with E. coli bacteremia, including an expansion in intermediate and non-classical monocytes, and increased caspase-1 activation in non-classical monocytes. In contrast, these changes were not observed in patients with S. aureus bacteremia. Additionally, we found differences in myeloid cell subset frequencies and caspase-1 activation between patients with and without sepsis, revealing distinct profiles associated with disease severity. Importantly, the differences in myeloid cell subsets and caspase-1 activation between E. coli and S. aureus bacteremia were primarily attributable to the infecting bacteria rather than disease severity. Furthermore, our findings suggest that eosinophil counts, and caspase-1 activation may serve as potential markers to distinguish between bacterial BSI and viral infections. Overall, our study highlights the importance of considering both the infecting pathogen and disease severity when studying the host immune response during bacteremia and suggests that potential innate immune biomarkers may improve the diagnosis and clinical management of BSI. In translational immunology studies conducted in intensive care units on sepsis, microbiological data are often inconsistently reported, and the investigation of innate or adaptive immune responses based on the etiologic agent involved is scarce. Here, we show that during bacteremia, the abundance of specific subtypes of circulating myeloid cells, such as non-classical monocytes, as well as their caspase 1 activation, differ depending on the causative bacteria, highlighting pathogen-specific immune signatures with potential diagnostic and therapeutic relevance.