Τίτλος:
Differential response induced by LPS and MPLA in immunocompetent and septic individuals
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA) induce, overall, similar transcriptional profiles in healthy individuals, although LPS has been shown to more potently induce pro-inflammatory cytokines. We explore herein whether MPLA could be considered as a synthetic replacement of LPS in immune functional assays to study anergy of immune cells in septic patients. Ex vivo whole blood stimulation with MPLA revealed a lower induction of the TNFα secreted protein in 20 septic patients (SP) compared to 10 healthy volunteers (HV), in agreement with monocyte anergy. Principal component analysis of the 93-gene molecular response to MPLA and LPS stimulation found that the main variability was driven by stimulation in HV and by pathophysiology in SP. MPLA was a stronger inducer of the HLA family genes than LPS in both populations, arguing for divergent signalling pathways downstream of TLR-4. In addition, MPLA appeared to present a more informative stratification potential within the septic population. © 2021
Συγγραφείς:
Albert Vega, C.
Karakike, E.
Bartolo, F.
Mouton, W.
Cerrato, E.
Brengel-Pesce, K.
Giamarellos-Bourboulis, E.J.
Mallet, F.
Trouillet-Assant, S.
Περιοδικό:
Clinical Immunology Newsletter
Εκδότης:
Academic Press Inc.
Λέξεις-κλειδιά:
C reactive protein; CD14 antigen; CD209 antigen; CD3 antigen; CD74 antigen; HLA antigen; HLA DM antigen; HLA DPA1 antigen; HLA DPB1 antigen; HLA DR antigen; interleukin 18; lapretolimod; lipopolysaccharide; protein kinase Mer; toll like receptor 4; tumor necrosis factor; unclassified drug; cytokine; lapretolimod; lipid A; lipopolysaccharide; toll like receptor 4; tumor necrosis factor, abdominal infection; ADRGE3 gene; adult; aged; APACHE; Article; blood; CD4+ T lymphocyte; CD8+ T lymphocyte; cell interaction; Charlson Comorbidity Index; clinical article; community acquired infection; controlled study; cytokine release; disease severity; ex vivo study; flow cytometry; gene; Gram negative sepsis; HLA system; human; immune response; immunocompetent cell; monocyte; pathophysiology; phenotype; pneumonia; principal component analysis; priority journal; prospective study; sepsis; Sequential Organ Failure Assessment Score; signal transduction; transcriptomics; clinical trial; female; immunocompromised patient; immunology; inflammation; male; randomized controlled trial; sepsis; very elderly, Aged; Aged, 80 and over; Cytokines; Female; Humans; Immunocompromised Host; Inflammation; Lipid A; Lipopolysaccharides; Male; Monocytes; Prospective Studies; Sepsis; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha
DOI:
10.1016/j.clim.2021.108714
