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TLR4 agonist activity of Alcaligenes lipid a utilizes MyD88 and TRIF signaling pathways for efficient antigen presentation and T cell differentiation by dendritic cells.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2023 Apr; Vol. 117, pp. 109852. Date of Electronic Publication: 2023 Feb 18. - Publication Year :
- 2023
-
Abstract
- Alcaligenes faecalis was previously identified as an intestinal lymphoid tissue-resident commensal bacteria, and our subsequent studies showed that lipopolysaccharide and its core active element (i.e., lipid A) have a potent adjuvant activity to promote preferentially antigen-specific Th17 response and antibody production. Here, we compared A. faecalis lipid A (ALA) with monophosphoryl lipid A, a licensed lipid A-based adjuvant, to elucidate the immunological mechanism underlying the adjuvant properties of ALA. Compared with monophosphoryl lipid A, ALA induced higher levels of MHC class II molecules and costimulatory CD40, CD80, and CD86 on dendritic cells (DCs), which in turn resulted in strong T cell activation. Moreover, ALA more effectively promoted the production of IL-6 and IL-23 from DCs than did monophosphoryl lipid A, thus leading to preferential induction of Th17 and Th1 cells. As underlying mechanisms, we found that the ALA-TLR4 axis stimulated both MyD88- and TRIF-mediated signaling pathways, whereas monophosphoryl lipid A was biased toward TRIF signaling. These findings revealed the effects of ALA on DCs and T cells and its induction pattern on signaling pathways.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Toll-Like Receptor 4 metabolism
Antigen Presentation
Alcaligenes metabolism
Signal Transduction
Adjuvants, Immunologic pharmacology
Cell Differentiation
Adaptor Proteins, Vesicular Transport metabolism
Dendritic Cells
Lipid A pharmacology
Lipid A metabolism
Myeloid Differentiation Factor 88 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 117
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 36806039
- Full Text :
- https://doi.org/10.1016/j.intimp.2023.109852