Differential response induced by LPS and MPLA in immunocompetent and septic individuals

• Published in: Clinical immunology (Orlando, Fla.) Vol. 226; p. 108714
• Main Authors: Albert Vega, Chloé, Karakike, Eleni, Bartolo, François, Mouton, William, Cerrato, Elisabeth, Brengel-Pesce, Karen, Giamarellos-Bourboulis, Evangelos J., Mallet, François, Trouillet-Assant, Sophie
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2021
• Subjects: Immune functional assay; LPS; MPLA; Sepsis; Septic patients; Stratification; Immune functional assay; Sepsis; MPLA; Stratification; LPS; Septic patients
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2021.108714

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.