Evaluation of TREM1 gene expression in circulating polymorphonuclear leukocytes and its inverse correlation with the severity of pathophysiological conditions in patients with acute bacterial infections

Abstract

During bacterial infection, activated polymorphonuclear leukocytes (PMNs) often cause inflammation and organ dysfunction in severely ill patients. Gene expression was analyzed in circulating PMNs isolated from these patients to determine the distinct expression profile. We focused on immunomodulatory genes, such as those for pattern recognition receptors, inflammatory cytokines, PMN surface antigens, and myeloid cell receptors in PMNs. Gene expression in 23 patients (12 with pneumonia and 11 with sepsis) were analyzed using quantitative real-time polymerase chain reaction. The mRNA levels of TLR2 (20/23 cases) and CD14 (18/23 cases) were upregulated in the PMNs of patients when compared with healthy subjects. The mRNA expression levels of TLR4 (16/23 cases) and IL6 (16/23 cases) were downregulated in patients' PMNs, and of TNFA (16/23 cases) were upregulated in these cells. Although mRNA levels of IL8RA (15/23 cases) were downregulated in PMNs, MAC-1 mRNA levels (14/23 cases) were upregulated in the same cells. Copies of the TREM1 transcript were 0.7- to 2.1-fold higher in patients with moderate pneumonia than in the healthy subjects; the average fold change was 1.1. The mRNA levels were 0.3-fold lower in the patients with severe pneumonia and sepsis than in the healthy subjects. In conclusion, the downregulation of TREM1 expression in PMNs is associated with the severity of the pathophysiological conditions and may be used as a surrogate marker of acute bacterial infections.