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

Clin Immunol. 2021 May;226:108714. doi: 10.1016/j.clim.2021.108714. Epub 2021 Mar 16.

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.

Keywords: Immune functional assay; LPS; MPLA; Sepsis; Septic patients; Stratification.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cytokines / immunology
  • Female
  • Humans
  • Immunocompromised Host / immunology*
  • Inflammation / immunology
  • Lipid A / analogs & derivatives*
  • Lipid A / immunology
  • Lipopolysaccharides / immunology*
  • Male
  • Monocytes / immunology
  • Prospective Studies
  • Sepsis / immunology*
  • Signal Transduction / immunology
  • Toll-Like Receptor 4 / immunology
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Cytokines
  • Lipid A
  • Lipopolysaccharides
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • monophosphoryl lipid A