Potent phagocytic activity with impaired antigen presentation identifying lipopolysaccharide-tolerant human monocytes: demonstration in isolated monocytes from cystic fibrosis patients.

摘要: Monocyte exposure to LPS induces a transient state in which these cells are refractory further endotoxin stimulation. This phenomenon, termed tolerance (ET), is characterized by decreased production of cytokines response the proinflammatory stimulus. We have established robust model ET and determined time frame features unresponsiveness cultured human monocytes. A large number genes transcribed tolerant monocytes were classified as either “tolerizable” or “nontolerizable” depending on their expression levels during phase. Tolerant exhibit rapid IL-1R-associated kinase-M (IRAK-M) overexpression, high triggering receptor expressed myeloid cells-1 (TREM-1) CD64, marked down-regulation MHC molecules NF-κB2. These combine potent phagocytic activity with impaired capability for Ag presentation. also show that circulating isolated from cystic fibrosis patients share all determinants characterize locked an state. findings identify new mechanism contributes inflammation despite frequency infections. Our results indicate phenotype interferes timing, efficiency, outcome innate immune responses against bacterial