title: TLR7 and TLR9 ligands regulate antigen presentation by macrophages.
abstract: 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.
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore 138648, Singapore.
authors.forename: Teja
authors.initials: T
authors.lastname: Celhar
authors.affiliation: Grupo Biología del Macrófago, Departamento de Fisiología e Inmunología, Universitat de Barcelona, 08028 Barcelona, Spain.
authors.forename: Selma
authors.initials: S
authors.lastname: Pereira-Lopes
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore 138648, Singapore.
authors.forename: Susannah I
authors.initials: SI
authors.lastname: Thornhill
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore 138648, Singapore.
authors.forename: Hui Yin
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore 138648, Singapore.
authors.forename: Manprit K
authors.initials: MK
authors.lastname: Dhillon
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore 138648, Singapore.
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore 138648, Singapore Institute of Molecular and Cell Biology, A*STAR, Singapore 138673, Singapore.
authors.forename: John E
authors.initials: JE
authors.lastname: Connolly
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore NUS Immunology Program, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Lina H K
authors.initials: LH
authors.lastname: Lim
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore 138648, Singapore.
authors.forename: Subhra K
authors.initials: SK
authors.lastname: Biswas
authors.affiliation: Singapore Immunology Network, A*STAR, Singapore 138648, Singapore annamarie_fairhurst@immunol.a-star.edu.sg.
authors.forename: Anna-Marie
authors.initials: AM
authors.lastname: Fairhurst
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D008024:Ligands; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000819:agonists* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000235:genetics / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000235:genetics / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; C556062:IL10 protein, mouse; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D016753:Interleukin-10; D018664:Interleukin-12
keywords: TLR; activation; antigen presentation; macrophages