Inverse Relationship Between Lipopolysaccharide Concentration and Monocyte and Dendritic Cells Inflammatory Response

Dendritic cells (DCs) and monocytes are key immunoregulatory cells that link the innate and adaptive immune response. However, understanding of human cell-specific responses to different doses of stimuli including lipopolysaccharide (LPS) is limited. This study investigated the monocyte and classical DC (cDC)-specific, as well as the overall inflammatory response after exposure to varying doses of LPS. Fresh peripheral whole blood (n = 8) was used in an in vitro peripheral blood culture model to assess cDC and monocyte responses in coculture with varying doses of LPS (0.25, 0.5, 0.75, 1 μg/mL). cDC and monocyte cytokine responses were measured through flow cytometry. Supernatants collected from the in vitro model were used in a cytometric bead array to assess the overall inflammatory response. Exposure to all doses of LPS tested increased monocyte, cDC, and the overall leukocyte response. A dose-dependent reduction in cDC and monocyte cytokine production was also evident with higher LPS doses. This study demonstrates that cell-subset-specific responses are more susceptible to LPS exposure compared with the overall inflammatory response. Therefore, assays that assess cell-specific immune responses may be more beneficial to identify underlying pathophysiology of infection and inflammation.