Differential response induced by LPS and MPLA in immunocompetent and septic individuals
| Autor: | Elisabeth Cerrato, François Mallet, Karen Brengel-Pesce, François Bartolo, William Mouton, Evangelos J. Giamarellos-Bourboulis, Sophie Trouillet-Assant, Chloé Albert Vega, Eleni Karakike |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male Lipopolysaccharide Immunology Population Monophosphoryl Lipid A Stimulation Monocytes 03 medical and health sciences chemistry.chemical_compound Immunocompromised Host 0302 clinical medicine Immune system Sepsis medicine Immunology and Allergy Humans Prospective Studies education Aged Aged 80 and over Inflammation education.field_of_study business.industry Tumor Necrosis Factor-alpha Monocyte Toll-Like Receptor 4 030104 developmental biology medicine.anatomical_structure Lipid A chemistry Cytokines Tumor necrosis factor alpha Female business Ex vivo 030215 immunology Signal Transduction |
| Zdroj: | Clinical immunology (Orlando, Fla.). 226 |
| ISSN: | 1521-7035 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect