Enhancement of Adaptive Immunity by the Human Vaccine Adjuvant AS01 Depends on Activated Dendritic Cells

5-lipoxygenase (5-LO) pathway is the major source of potent proinflammatory leukotrienes (LTs) issued from the metabolism of arachidonic acid (AA), and best known for their roles in the pathogenesis of asthma. These lipid mediators are mainly released from myeloid cells and may act as physiological autocrine and paracrine signalling molecules, and play a central role in regulating the interaction between innate and adaptive immunity. The biological actions of LTs including their immunoregulatory and proinflammatory effects are mediated through extracellular specific G-protein-coupled receptors. Despite their role in inflammatory cells, such as neutrophils and macrophages, LTs may have important effects on dendritic cells (DC)-mediated adaptive immunity. Several lines of evidence show that DC not only are important source of LTs, but also become targets of their actions by producing other lipid mediators and proinflammatory molecules. This review focuses on advances in 5-LO pathway biology, the production of LTs from DC and their role on various cells of immune system and in adaptive immunity.

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Cationic DDA/TDB liposome as a mucosal vaccine adjuvant for uptake by dendritic cells in vitro induces potent humoural immunity

Artificial Cells Nanomedicine and Biotechnology ◽

10.1080/21691401.2018.1438450 ◽

2018 ◽

Vol 46 (sup1) ◽

pp. 852-860 ◽

Cited By ~ 9

Author(s):

Wenjing Qu ◽

Na Li ◽

Rui Yu ◽

Wenbao Zuo ◽

Tingting Fu ◽

...

Keyword(s):

Dendritic Cells ◽

Mucosal Vaccine ◽

Vaccine Adjuvant

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The Integrity of α-β-α Sandwich Conformation Is Essential for a Novel Adjuvant TFPR1 to Maintain Its Adjuvanticity

Biomolecules ◽

10.3390/biom9120869 ◽

2019 ◽

Vol 9 (12) ◽

pp. 869 ◽

Cited By ~ 1

Author(s):

Qiao Li ◽

Xiuzhe Ning ◽

Yuepeng Wang ◽

Qing Zhu ◽

Yan Guo ◽

...

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Peptide Vaccine ◽

Structural Basis ◽

Vaccine Adjuvant ◽

Novel Approach ◽

Immunologic Activity

TFPR1 is a novel peptide vaccine adjuvant we recently discovered. To define the structural basis and optimize its application as an adjuvant, we designed three different truncated fragments that have removed dominant B epitopes on TFPR1, and evaluated their capacity to activate bone marrow-derived dendritic cells and their adjuvanticity. Results demonstrated that the integrity of an α-β-α sandwich conformation is essential for TFPR1 to maintain its immunologic activity and adjuvanticity. We obtained a functional truncated fragment TFPR-ta ranging from 40–168 aa of triflin that has similar adjuvanticity as TFPR1 but with 2-log fold lower immunogenicity. These results demonstrated a novel approach to evaluate and improve the activity of protein-based vaccine adjuvant.

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Preface—Dendritic cells: Master regulators of innate and adaptive immunity

International Review of Cell and Molecular Biology - Immunobiology of Dendritic Cells Part A ◽

10.1016/s1937-6448(19)30095-4 ◽

2019 ◽

pp. ix-xiv

Author(s):

Claire Lhuillier ◽

Lorenzo Galluzzi

Keyword(s):

Dendritic Cells ◽

Adaptive Immunity ◽

Innate And Adaptive Immunity ◽

Master Regulators

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Staphylococcus aureusImpairs the Function of and Kills Human Dendritic Cells via the LukAB Toxin

mBio ◽

10.1128/mbio.01918-18 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 12

Author(s):

Evelien T. M. Berends ◽

Xuhui Zheng ◽

Erin E. Zwack ◽

Mickaël M. Ménager ◽

Michael Cammer ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Dendritic Cells ◽

Adaptive Immunity ◽

T Cell Activation ◽

Antigen Presenting Cells ◽

Infection Model ◽

High Morbidity ◽

Content Type ◽

Human Dendritic Cells ◽

Antigen Presenting

ABSTRACTStaphylococcus aureusis a human pathogen responsible for high morbidity and mortality worldwide. Recurrent infections with this bacterium are common, suggesting thatS. aureusthwarts the development of sterilizing immunity.S. aureusstrains that cause disease in humans produce up to five different bicomponent toxins (leukocidins) that target and lyse neutrophils, innate immune cells that represent the first line of defense againstS. aureusinfections. However, little is known about the role of leukocidins in blunting adaptive immunity. Here, we explored the effects of leukocidins on human dendritic cells (DCs), antigen-presenting cells required for the development of adaptive immunity. Using anex vivoinfection model of primary human monocyte-derived dendritic cells, we found thatS. aureus, including strains from different clonal complexes and drug resistance profiles, effectively kills DCs despite efficient phagocytosis. Although all purified leukocidins could kill DCs, infections with live bacteria revealed thatS. aureustargets and kills DCs primarily via the activity of leukocidin LukAB. Moreover, using coculture experiments performed with DCs and autologous CD4+T lymphocytes, we found that LukAB inhibits DC-mediated activation and proliferation of primary human T cells. Taken together, the data determined in the study reveal a novel immunosuppressive strategy ofS. aureuswhereby the bacterium blunts the development of adaptive immunity via LukAB-mediated injury of DCs.IMPORTANCEAntigen-presenting cells such as dendritic cells (DCs) fulfill an indispensable role in the development of adaptive immunity by producing proinflammatory cytokines and presenting microbial antigens to lymphocytes to trigger a faster, specific, and long-lasting immune response. Here, we studied the effect ofStaphylococcus aureustoxins on human DCs. We discovered that the leukocidin LukAB hinders the development of adaptive immunity by targeting human DCs. The ability ofS. aureusto blunt the function of DCs could help explain the high frequency of recurrentS. aureusinfections. Taken together, the results from this study suggest that therapeutically targeting theS. aureusleukocidins may boost effective innate and adaptive immune responses by protecting innate leukocytes, enabling proper antigen presentation and T cell activation.

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