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Updated: Apr 10, 2026
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
MPLA shows attenuated pro-inflammatory properties and diminished capacity to activate mast cells in comparison with
S Schülke1, A Flaczyk1, L Vogel2
1Vice President's Research Group 1: Molecular Allergology, Paul-Ehrlich-Institut, Langen, Germany.
Background:
Monophosphoryl lipid A (MPLA), a nontoxic TLR4 ligand derived from lipopolysaccharide (LPS), is used clinically as an adjuvant in cancer, hepatitis, and malaria vaccines and in allergen-specific immunotherapy. Nevertheless, its cell-activating effects have not been analyzed in a comprehensive direct comparison including a wide range of different immune cells. Therefore, the objective of this study was the side-by-side comparison of the immune-modulating properties of MPLA and LPS on different immune cells.
Methods:
Immune-activating properties of MPLA and LPS were compared in human monocytes and mast cells (MCs), a mouse endotoxin shock model (ESM), and mouse bone marrow (BM)-derived myeloid dendritic cells (mDCs), T cells (TCs), B cells, and MCs.
Results:
In a mouse in vivo ESM and a human ex vivo monocyte activation test (MAT), MPLA induced the same cytokine secretion pattern as LPS (ESM: IL-6, IL-12, TNF-α; MAT: IL-1β, IL-6, TNF-α), albeit at lower levels. Mouse mDCs and ex vivo isolated B cells stimulated with MPLA required a higher threshold to induce TRIF-dependent cytokine secretion (IL-1β, IL-6, IL-10, and TNF-α) than did LPS-stimulated cells. In mDC:DO11.10 CD4 TC cocultures, stimulation with MPLA, but not with LPS, resulted in enhanced OVA-specific IL-4 and IL-5 secretion from DO11.10 CD4 TCs. Unexpectedly, in both human and mouse MCs, MPLA, unlike LPS, did not elicit secretion of pro-inflammatory cytokines.
Conclusions:
Compared to LPS, MPLA induced a qualitatively similar, but less potent pro-inflammatory immune response, but was unable to activate human or mouse MCs.
Insights
Monophosphoryl lipid A (MPLA) and lipopolysaccharide (LPS) activate immune cells similarly but MPLA is less potent. MPLA did not activate mast cells, unlike LPS, suggesting differential immune modulation.
Area of Science:
- Immunology
- Vaccine Adjuvants
- Toll-like Receptor Signaling
Background:
- Monophosphoryl lipid A (MPLA) is a clinically used, non-toxic TLR4 ligand derived from lipopolysaccharide (LPS).
- MPLA serves as an adjuvant in vaccines for cancer, hepatitis, and malaria, and in allergen immunotherapy.
- A comprehensive comparison of MPLA and LPS on diverse immune cells is lacking.
Purpose of the Study:
- To conduct a side-by-side comparison of the immune-modulating properties of MPLA and LPS.
- To investigate the differential effects of MPLA and LPS on various human and mouse immune cells.
Main Methods:
- Compared immune activation by MPLA and LPS in human monocytes and mast cells (MCs).
- Utilized a mouse endotoxin shock model (ESM) and analyzed mouse bone marrow-derived myeloid dendritic cells (mDCs), T cells (TCs), B cells, and MCs.
- Assessed cytokine secretion patterns and cell activation thresholds in response to MPLA and LPS stimulation.
Main Results:
- MPLA induced a similar cytokine profile as LPS in mouse ESM and human monocytes, but at lower levels.
- MPLA required a higher threshold for TRIF-dependent cytokine secretion in mouse mDCs and B cells compared to LPS.
- MPLA, but not LPS, enhanced OVA-specific IL-4 and IL-5 secretion in mDC:DO11.10 CD4 TC cocultures.
- MPLA failed to induce pro-inflammatory cytokine secretion in both human and mouse mast cells, unlike LPS.
Conclusions:
- MPLA elicits a qualitatively similar but less potent pro-inflammatory immune response compared to LPS.
- MPLA demonstrates differential immune cell activation, notably failing to activate mast cells.
- These findings highlight distinct immunomodulatory profiles of MPLA and LPS, relevant for vaccine and immunotherapy development.
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