Differences in TLR7/8 activation between monocytes and macrophages

Eng, Hock‐Liew; Hsu, Yuan-Ying; Lin, Tzu-Chao

doi:10.1016/j.bbrc.2018.02.079

Cited by 29 publications

(27 citation statements)

References 20 publications

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“…R837 is an immune adjuvant that is able to trigger the maturation of APCs . PLGA NPs were utilized to encapsulate R837 to formulate nanoparticles of different sizes by adjusting the shear forces and the concentration of PLGA .…”

Section: Resultsmentioning

confidence: 99%

Multiantigenic Nanoformulations Activate Anticancer Immunity Depending on Size

Feng

Wang

et al. 2019

Adv Funct Materials

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Nanoparticle-adjuvanted cancer vaccines are attracting increasing attention because they can induce an effective anticancer immune response. Singleantigen vaccines are inefficient to inhibit cancer progression due to the heterogeneity of tumors and the antigenicity alteration of tumor-associated antigens. Therefore, the efficient delivery of multiple antigens to antigen-presenting cells is an excellent opportunity for strong anticancer immunity. In this study, three immunoadjuvant-loaded multiantigenic nanoparticles MANPs/R837 with different diameters, i.e., 83, 103, and 122 nm, are prepared through coating of the cancer cell membrane as a source of multiple antigens onto the imiquimod R837-loaded poly(lactic-co-glycolic acid) nanoparticles. The MANP/R837 with a diameter of 83 nm (MANP83/R837) shows the most efficient delivery of the payload to the draining lymph nodes and achieves the best antigen presentation to T lymphocytes. Compared with the other two nanovaccines, MANP83/ R837 has a stronger inhibitory effect on tumor growth and metastasis. In the combination therapy with checkpoint blockade therapy using programmed cell death-1 antibody, MANPs/R837 show effective inhibition against tumor progression, and MANP83/R837 achieves the most exciting effect. Therefore, MANPs/ R837, as a promising therapeutic cancer vaccine, demonstrates great prospects in cancer immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Multiantigenic Nanoformulations Activate Anticancer Immunity Depending on Size

Feng

Wang

et al. 2019

Adv Funct Materials

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“…Such higher intracellular delivery of IMQ would be responsible for increased cytokines production by nanoARC-IMQ compared to IMQ. The IMQ is known to activate macrophages and other immune cells by inducing local cytokines some of which are crucial for maturation of APCs such as IFN-α, TNF-α, IL-1α, IL-1b, IL-6, IL-8, IL-10, via MyD88-dependent signaling pathway (Eng et al, 2018 ) with a threshold concentration for human peripheral blood monocyte cell PBMCs included macrophages of 0.5 μg/ml (~2 μM) (Gibson et al, 1995 ; Testerman et al, 1995 ; Stanley, 2002 ). Besides, upon SR-A1 ligand internalization, RAW264.7 macrophages induce TNF-α, IL-6, and other proinflammatory and anti-inflammatory cytokines such as IL-10 in a pattern depending on the type of ligand (Coller and Paulnock, 2001 ).…”

Section: Discussionmentioning

confidence: 99%

Make It Simple: (SR-A1+TLR7) Macrophage Targeted NANOarchaeosomes

Parra

Caimi

Altube

et al. 2018

Front. Bioeng. Biotechnol.

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Hyperhalophilic archaebacteria exclusively produce sn2,3 diphytanylglycerol diether archaeolipids, unique structures absent in bacteria and eukaryotes. Nanovesicles made of archaeolipids known as nanoarchaeosomes (nanoARC), possess highly stable bilayers, some of them displaying specific targeting ability. Here we hypothesize that nanoARC made from Halorubrum tebenquichense archaebacteria, may constitute efficient carriers for the TLR7 agonist imiquimod (IMQ). NanoARC-IMQ takes advantage of the intense interaction between IMQ and the highly disordered, poorly fluid branched archaeolipid bilayers, rich in archaeol analog of methyl ester of phosphatidylglycerophosphate (PGP-Me), a natural ligand of scavenger receptor A1 (SR-A1). This approach lacks complex manufacture steps required for bilayers labeling, enabling future analytical characterization, batch reproducibility, and adaptation to higher scale production. SR-A1 mediated internalization of particulate material is mostly targeted to macrophages and is extensive because it is not submitted to a negative feedback. A massive and selective intracellular delivery of IMQ may concentrate its effect specifically into the endosomes, where the TLR7 is expressed, magnifying its immunogenicity, at the same time reducing its systemic bioavailability, and therefore it's in vivo adverse effects. NanoARC-IMQ (600–900 nm diameter oligolamellar vesicles of ~−43 mV Z potential) were heavily loaded with IMQ at ~44 μg IMQ/mg phospholipids [~20 folds higher than the non-SR-A1 ligand soyPC liposomes loaded with IMQ (LIPO-IMQ)]. In vitro, nanoARC-IMQ induced higher TNF-α and IL-6 secretion by J774A1 macrophages compared to same dose of IMQ and same lipid dose of LIPO-IMQ. In vivo, 3 subcutaneous doses of nanoARC-IMQ+ 10 μg total leishmania antigens (TLA) at 50 μg IMQ per Balb/C mice, induced more pronounced DTH response, accompanied by a nearly 2 orders higher antigen-specific systemic IgG titers than IMQ+TLA and LIPO-IMQ. The isotype ratio of nanoARC-IMQ+TLA remained ~0.5 indicating, the same as IMQ+TLA, a Th2 biased response distinguished by a pronounced increase in antibody titers, without negative effects on splenocytes lymphoproliferation, with a potential CD8+LT induction 10 days after the last dose. Overall, this first approach showed that highly SR-A1 mediated internalization of heavily loaded nanoARC-IMQ, magnified the effect of IMQ on TLR7 expressing macrophages, leading to a more intense in vivo immune response.

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“…The effect of the circulating EVs' miRNAs on blood immune cells in our study indicated the systemic immune response. However, it is reported that ssRNA molecules can promote the monocyte activation and differentiation into tissue macrophages (Krutzik et al, 2005;Saha et al, 2017), which can infiltrate into the affected target tissues (Eng et al, 2018), resulting in an enhanced local immune response. Moreover, Langerhans islets contain resident macrophages that hold an essential role in the local islet immunity, development of acute insulitis, and FIGURE 7 | Chloroquine miRNA/DOTAP inhibition.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Derived Human-miRNAs Modulate the Immune System in Type 1 Diabetes

Tesovnik

Kovač

Pohar

et al. 2020

Front. Cell Dev. Biol.

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Extracellular vesicles with their molecular cargo can modulate target cell response and may affect the pathogenesis of diseases. The extracellular vesicles containing micro-RNAs (miRNAs), which are often studied as disease biomarkers, but rarely as mediators of the disease development. The role of extracellular vesicles derived miRNAs in type 1 diabetes is currently not well established. We observed a fraction of blood plasma extracellular vesicles positive for membrane proteins potentially associated with insulinproducing beta-cells and identified differentially expressed extracellular vesicles derived miRNAs in individuals with type 1 diabetes. These differentially expressed extracellular vesicles derived human miRNAs in participants with type 1 diabetes and participants with Langerhans islets beta-cells destruction showed the ability to activate TLR7/8 signaling cascade and increase activation as well as cytotoxicity of the effector blood immune cells with cytokine and chemokine release. Our results illustrate extracellular vesicles derived human miRNAs as modulators of the immune system in type 1 diabetes autoimmunity, providing potentially new insight into the pathogenesis of the disease, and novel molecular targets for intervention and type 1 diabetes prevention.

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Differences in TLR7/8 activation between monocytes and macrophages

Cited by 29 publications

References 20 publications

Multiantigenic Nanoformulations Activate Anticancer Immunity Depending on Size

Multiantigenic Nanoformulations Activate Anticancer Immunity Depending on Size

Make It Simple: (SR-A1+TLR7) Macrophage Targeted NANOarchaeosomes

Extracellular Vesicles Derived Human-miRNAs Modulate the Immune System in Type 1 Diabetes

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