TLR7 and TLR9 ligands regulate antigen presentation by macrophages
Open accessAbstract
The toll-like receptors (TLRs) are important innate receptors recognizing potentially pathogenic material. However, they also play a significant role in the development of Alzheimer’s disease, cancer, autoimmunity and the susceptibility to viral infections. Macrophages are essential for an effective immune response to foreign material and the resolution of inflammation. In these studies, we examined the impact of different TLR ligands on macrophage cell function. We demonstrate that stimulation of all TLRs tested increases the phagocytosis of apoptotic cells by macrophages. TLR7 and TLR9 ligation decreased the levels of the surface co-expression molecules CD86 and MHCII, which was associated with a concomitant reduction in antigen presentation and proliferation of T cells. This down-regulation in macrophage function was not due to an increase in cell death. In fact, exposure to TLR7 or TLR9 ligands promoted cell viability for up to 9 days, in contrast to TLR3 or TLR4. Additionally, macrophages exposed to TLR7/TLR9 ligands had a significantly lower ratio of Il-12/Il-10 mRNA expression compared with those treated with the TLR4 ligand, LPS. Taken together, these data demonstrate that TLR7/TLR9 ligands push the macrophage into a phagocytic long-lived cell, with a decreased capacity of antigen presentation and reminiscent of the M2 polarized state.
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- Authors
- Celhar, T., Pereira-Lopes, S., Thornhill, S. I., Lee, H. Y., Dhillon, M. K., Poidinger, M., Connolly, J. E., Lim, L. H. K., Biswas, S. K., & Fairhurst, A.-M.
- Affiliations
- Agency for Science, Technology and Research (SG)
- Grupo Biología del Macrófago, Departamento de Fisiología e Inmunología, Universitat de Barcelona 2 , 08028 Barcelona , Spain
- National University of Singapore (SG)
- Venue
- International Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-11-13
- Volume
- 28
- Issue
- 5
- Pages
- 223-232
- ISSN
- 0953-8178 (ISSN-L)
- 1460-2377
- PMC
- PMC4888346
- OpenAlex
- W2173447488
- Cited by
- 52
- References
- 41
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 13 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 2 · 2016: 2
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- International Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National University of Singapore
- National Medical Research Council
- Institute of Molecular and Cell Biology
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- TLR7, TLR9, Toll-like receptor ligands, macrophages, antigen presentation, phagocytosis of apoptotic cells, CD86, MHC class II, T cell proliferation, macrophage viability, M2 macrophage polarization, TLR3, TLR4, lipopolysaccharide
- MeSH terms
- Animals, Histocompatibility Antigens Class II, Gene Expression Regulation, Ligands, Lipopolysaccharides, Macrophages, Membrane Glycoproteins, Phagocytosis, Interleukin-10, Antigen Presentation, Mice, Knockout, Interleukin-12, Toll-Like Receptor 7, Toll-Like Receptor 9, Mice
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