@article{2999888,
    title = "Differential response induced by LPS and MPLA in immunocompetent and septic individuals",
    author = "Albert Vega, C. and Karakike, E. and Bartolo, F. and Mouton, W. and Cerrato, E. and Brengel-Pesce, K. and Giamarellos-Bourboulis, E.J. and Mallet, F. and Trouillet-Assant, S.",
    journal = "Clinical Immunology Newsletter",
    year = "2021",
    volume = "226",
    publisher = "Academic Press Inc.",
    issn = "0197-1859",
    doi = "10.1016/j.clim.2021.108714",
    keywords = "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",
    abstract = "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"
}