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.

中文翻译：

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脂多糖浓度与单核细胞和树突细胞炎症反应之间的反比关系。

树突状细胞（DC）和单核细胞是连接先天性和适应性免疫反应的关键免疫调节细胞。但是，对人类细胞对包括脂多糖（LPS）在内的不同剂量刺激的特异性反应的了解是有限的。这项研究调查了单核细胞和经典DC（cDC）的特异性，以及暴露于不同剂量LPS​​后的整体炎症反应。新鲜的外周全血（n  = 8）用于体外外周血培养模型，以评估不同剂量LPS​​（0.25、0.5、0.75、1μg/ mL）共培养中的cDC和单核细胞反应。通过流式细胞仪测量cDC和单核细胞的细胞因子反应。从体外收集的上清液将模型用于细胞计数珠阵列中以评估总体炎症反应。暴露于所有剂量的LPS均可增加单核细胞，cDC和总白细胞反应。LPS剂量较高时，cDC和单核细胞细胞因子产生的剂量依赖性降低也很明显。这项研究表明，与总体炎症反应相比，特定于细胞亚群的反应对LPS暴露更敏感。因此，评估细胞特异性免疫反应的测定法可能对识别感染和炎症的潜在病理生理学更为有益。