Silencing Triggering Receptors Expressed on Myeloid Cells-1 Impaired the Inflammatory Response to Oxidized Low-Density Lipoprotein in Macrophages

Li, Houxuan; Hong, Feifei; Pan, Shengbo; Lei, Lang; Yan, Fuhua

doi:10.1007/s10753-015-0239-5

Cited by 18 publications

(13 citation statements)

References 38 publications

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“…Mice treated by intrathecal administration of MIS416 (n = 17), at EAE onset, progressed less rapidly following 2 days than control animals(n = 12). c Cells isolated from brains of mice with EAE were analyzed by flow cytometry, at 24 h post intrathecal administration of MIS416 (n = [8][9][10][11][12][13][14][15][16][17][18][19]. Bar graph shows MIS416-induced recruitment of CD45 high cells in the CNS.…”

Section: Discussionmentioning

confidence: 99%

“…Increased phagocytic activity was supported by RNAseq data from MIS416-treated CNS, which showed upregulated levels of phagocytosis related genes, including MSR1 and TREM1. These are known to be expressed by monocytes and act as positive regulators of phagocytosis in these cells [8,15]. Extraparenchymal myeloid cells would be expected to take up MIS416 microparticles directly upon encounter in leptomeningeal space.…”

Section: Discussionmentioning

confidence: 99%

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Innate signaling within the central nervous system recruits protective neutrophils

Khorooshi

Marczynska

Dieu

et al. 2020

acta neuropathol commun

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There is great interest in understanding how the central nervous system (CNS) communicates with the immune system for recruitment of protective responses. Infiltrating phagocytic monocytes and granulocytes are implicated in neuroinflammation in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). To investigate how CNS endogenous signals can be harnessed to promote anti-inflammatory programs, we have used a particulate Toll-like receptor 9 and nucleotide-oligomerization domain 2 bispecific innate ligand (MIS416), to address whether its phagocytosis within the CNS recruits protective myeloid cells. We find that MIS416 injected intrathecally into the cerebrospinal fluid via the cisterna magna induced a local chemokine response that recruited blood-derived monocytes and neutrophils to the CNS. These cells phagocytosed MIS416. The increase in EAE severity normally seen from time of onset did not occur in mice receiving MIS416. This suppression of disease symptoms was dependent on expression of the type I interferon receptor (IFNAR). Transfer of intrathecal MIS416induced neutrophils suppressed EAE in recipient mice, while monocytes did not transfer protection. MIS416induced neutrophils showed increased IL-10 expression that was IFNAR1-driven. In contrast to intrathecal administration, intravenous administration of MIS416 led to monocyte but not neutrophil infiltration to the CNS. We thus identify a CNS-intrinsic and-specific phagocytosis-induced recruitment of anti-inflammatory neutrophils that contribute to CNS homeostasis and may have therapeutic potential.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Innate signaling within the central nervous system recruits protective neutrophils

Khorooshi

Marczynska

Dieu

et al. 2020

acta neuropathol commun

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“…TREM‐1 connected and regulated complicated signals through several pattern recognition receptors induced by specific toll‐like receptor agonists in the inflammatory process 7, 8. Li et al27 identified that TREM‐1 was a certain epitope of oxidized low‐density lipoprotein in macrophages through the toll‐like receptor pathway, which facilitated foam cell formation and activated inflammatory response, suggesting a crucial role in further plaque progression and rupture. Silencing TREM‐1 by means of short hairpin RNA or linear plasmid 17 reduced lipid uptake and foam cell formation and impaired inflammatory response to oxidized low‐density lipoprotein 27.…”

Section: Discussionmentioning

confidence: 99%

“…Li et al27 identified that TREM‐1 was a certain epitope of oxidized low‐density lipoprotein in macrophages through the toll‐like receptor pathway, which facilitated foam cell formation and activated inflammatory response, suggesting a crucial role in further plaque progression and rupture. Silencing TREM‐1 by means of short hairpin RNA or linear plasmid 17 reduced lipid uptake and foam cell formation and impaired inflammatory response to oxidized low‐density lipoprotein 27. The expression of TREM‐1 was also mostly found close to cholesterol‐ and necrotic‐rich areas.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Utility of Soluble TREM‐1 in Predicting Mortality and Cardiovascular Events in Patients With Acute Myocardial Infarction

Wang

Tang

Shen

et al. 2018

JAHA

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BackgroundTriggering receptor expressed on myeloid cells‐1 (TREM‐1) is thought to be critical for inflammatory signal amplification and involved in the development of atherosclerosis. TREM‐1 is significantly increased in patients with myocardial infarction. The aim of this study was to investigate the association between soluble TREM‐1 (sTREM‐1) and mortality and cardiovascular events in patients with acute myocardial infarction.Methods and ResultsWe included 838 consecutive patients with acute myocardial infarction from October 7, 2012 to December 5, 2014. Blood samples were collected from patients with acute myocardial infarction immediately after diagnosis. During follow‐up, 88 patients died, and 180 patients reached the combined end points of major adverse cardiovascular event (MACE). Patients with high sTREM‐1 (higher than the median) had increased risk of all‐cause mortality and MACE compared with those with low sTREM‐1 (log‐rank test, P<0.001). After adjustment for confounding risk factors by Cox regression analysis, high sTREM‐1 remained an independent predictor of all‐cause mortality (hazard ratio, 1.978; 95% confidence interval, 1.462–2.675; P<0.001) and MACE (hazard ratio, 2.413; 95% confidence interval, 2.022–2.879; P<0.001). After the addition of sTREM‐1 to the reference model, the C‐statistic for all‐cause mortality increased from 0.86 to 0.89, and the difference was 0.023 (95% confidence interval, 0.0009–0.0477), and the C‐statistic for MACE increased from 0.71 to 0.80, and the difference was 0.087 (95% confidence interval, 0.053–0.122). sTREM‐1 levels were consistently positively associated with risks of all‐cause mortality and MACE in various subpopulations, and there was no significant interaction among prespecified subgroups.Conclusions sTREM‐1 was significantly associated with all‐cause mortality and MACE, independent of established conventional risk factors in patients with acute myocardial infarction.

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“…It has been postulated that the association between microbial infection and atherosclerosis involves common mechanisms of signaling via TLR2 and TLR4. Some investigators have proposed that TLR signaling induced by multiple pathogens and endogenous ligands may explain the link to atherosclerosis and that therapeutic TLR antagonism could prove beneficial in the treatment of chronic atherosclerosis (13, 14, 116–118). However, our work revealed that P. gingivalis -mediated TLR4 signaling protects from atherosclerosis, suggesting that effects are pathogen specific.…”

Section: Innate Immune Mechanisms Linking Specific Microorganisms To mentioning

confidence: 99%

Microbiota, Immune Subversion, and Chronic Inflammation

Kramer

Genco

2017

Front. Immunol.

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Several host-adapted pathogens and commensals have evolved mechanisms to evade the host innate immune system inducing a state of low-grade inflammation. Epidemiological studies have also documented the association of a subset of these microorganisms with chronic inflammatory disorders. In this review, we summarize recent studies demonstrating the role of the microbiota in chronic inflammatory diseases and discuss how specific microorganisms subvert or inhibit protective signaling normally induced by toll-like receptors (TLRs). We highlight our work on the oral pathogen Porphyromonas gingivalis and discuss the role of microbial modulation of lipid A structures in evasion of TLR4 signaling and resulting systemic immunopathology associated with atherosclerosis. P. gingivalis intrinsically expresses underacylated lipid A moieties and can modify the phosphorylation of lipid A, leading to altered TLR4 signaling. Using P. gingivalis mutant strains expressing distinct lipid A moieties, we demonstrated that expression of antagonist lipid A was associated with P. gingivalis-mediated systemic inflammation and immunopathology, whereas strains expressing agonist lipid A exhibited modest systemic inflammation. Likewise, mice deficient in TLR4 were more susceptible to vascular inflammation after oral infection with P. gingivalis wild-type strain compared to mice possessing functional TLR4. Collectively, our studies support a role for P. gingivalis-mediated dysregulation of innate and adaptive responses resulting in immunopathology and systemic inflammation. We propose that anti-TLR4 interventions must be designed with caution, given the balance between the protective and destructive roles of TLR signaling in response to microbiota and associated immunopathologies.

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Silencing Triggering Receptors Expressed on Myeloid Cells-1 Impaired the Inflammatory Response to Oxidized Low-Density Lipoprotein in Macrophages

Cited by 18 publications

References 38 publications

Innate signaling within the central nervous system recruits protective neutrophils

Innate signaling within the central nervous system recruits protective neutrophils

Prognostic Utility of Soluble TREM‐1 in Predicting Mortality and Cardiovascular Events in Patients With Acute Myocardial Infarction

Microbiota, Immune Subversion, and Chronic Inflammation

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