ABSTRACT
Objective To measure the reads numbers of Human Herpes Virus in blood sample from patients with sepsis by using Next Generation sequencing (NGS) and explore the relationship between read number of virus and the severity, prognosis, immune status of septic patients.Methods Blood sample and clinical information from 150 patients with sepsis were enrolled in this study. All patients' blood samples were sent to perform NGS pathogenic test. According to the results of NGS, septic patients were divided into HHV-detected group and HHV-undetected group. Besides, patients were scored with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ ) on the day of blood collection. The counts of total leukocytes, lymphocytes and the levels of cytokines were also measured. Results 51.3 percent of septic patients were detected with HHV nucleic acid. The APACHE Ⅱ and SOFA scores were significantly higher in HHV-detected patients compared with patients in HHV-undetected group. Besides, patients who had a higher SOFA score might lead to a higher detection rate of HHV. Moreover, the 28-day and 90-day mortality rates were higher in detected group (P< 0.01). The detection of HHV nucleic acid was positively correlated with a high 90-day mortality rate (P= 0.0056). One-way analysis of variance revealed that the counts of total lymphocyte and different types of lymphocyte (CD19+B、CD4+T、CD8+T、CD56+ lymphocyte) were significantly less in detected group than that in undetected group. Furthermore, both the levels of pro-inflammatory cytokines (TNF-α、IL-2R、IL-6、IL-8) and anti-inflammatory cytokines (IL-10) in detected group were significantly higher than those in undetected group. Gender, age, APACHE Ⅱ , SOFA, IL-2R, IL-10, CD19+B lymphocyte and T cells, were still significant even after multivariate logistic analyses. Conclusions The detection rate of HHV nucleic acid in patients with sepsis was high. The detection of HHV was a high-risk factor of death in patients with sepsis. The cut-off value which is more than 100 had a significant clinical value. The infection of HHV could be conducted by dysfunction of immunity.
ABSTRACT
Genetic mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to a variety of neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia and Parkinson’s disease. In the brain, TREM2 is highly expressed on the cell surface of microglia, where it can transduce signals to regulate microglial functions such as phagocytosis. To date, mechanisms underlying intracellular trafficking of TREM2 remain elusive. Mutations in the presenilin 1 (PS1) catalytic subunit of the γ-secretase complex have been associated with increased generation of the amyloidogenic Aβ (amyloid-β) 42 peptide through cleavage of the Aβ precursor amyloid precursor protein. Here we found that TREM2 interacts with PS1 in a manner independent of γ-secretase activity. Mutations in TREM2 alter its subcellular localization and affects its interaction with PS1. Upregulation of PS1 reduces, whereas downregulation of PS1 increases, steady-state levels of cell surface TREM2. Furthermore, PS1 overexpression results in attenuated phagocytic uptake of Aβ by microglia, which is reversed by TREM2 overexpression. Our data indicate a novel role for PS1 in regulating TREM2 intracellular trafficking and pathophysiological function.