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MPLA shows attenuated pro‐inflammatory properties and diminished capacity to activate mast cells in comparison with LPS
Author(s) -
Schülke S.,
Flaczyk A.,
Vogel L.,
Gaudenzio N.,
Angers I.,
Löschner B.,
Wolfheimer S.,
Spreitzer I.,
Qureshi S.,
Tsai M.,
Galli S.,
Vieths S.,
Scheurer S.
Publication year - 2015
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12675
Subject(s) - lipopolysaccharide , immune system , tumor necrosis factor alpha , cytokine , immunology , biology , monocyte , ex vivo , inflammation , in vivo , microbiology and biotechnology
Background Monophosphoryl lipid A ( MPLA ), a nontoxic TLR 4 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 ( MC s), a mouse endotoxin shock model ( ESM ), and mouse bone marrow ( BM )‐derived myeloid dendritic cells ( mDC s), T cells ( TC s), B cells, and MC s. 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 mDC s 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 : DO 11.10 CD 4 TC cocultures, stimulation with MPLA , but not with LPS , resulted in enhanced OVA ‐specific IL ‐4 and IL ‐5 secretion from DO 11.10 CD 4 TC s. Unexpectedly, in both human and mouse MC s, 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 MC s.