A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease

PrabhuDas, Mercy; Baldwin, Cynthia L.; Bollyky, Paul L.; Bowdish, Dawn M. E.; Drickamer, Kurt; Febbraio, Maria; Herz, Joachim; Kobzik, Lester; Krieger, Monty; Loike, John D.; McVicker, Benita L.; Means, Terry K.; Moestrup, Søren K.; Post, Steven R.; Sawamura, Tatsuya; Silverstein, Samuel C.; Speth, Robert C.; Telfer, Janice C.; Thiele, Geoffrey M.; Wang, Xiang Yang; Wright, Samuel D.; Khoury, Joseph El

doi:10.4049/jimmunol.1700373

Cited by 277 publications

(227 citation statements)

References 168 publications

(179 reference statements)

Supporting

Mentioning

204

Contrasting

Unclassified

Order By: Relevance

“…41 CD36 is involved in the recognition of a diverse array of pathological and physiological ligands, including members of a family of specific oxidized phospholipids, oxPC CD36 . 42 CD36 mediated the recognition of oxPC CD36 in oxidized LDL and subsequent binding and internalization of oxidized LDL by macrophages in the arterial wall contributes to atherogenesis in hyperlipidemic mice.…”

Section: Discussionmentioning

confidence: 99%

TLR2 Plays a Key Role in Platelet Hyperreactivity and Accelerated Thrombosis Associated With Hyperlipidemia

Biswas

Zimman

Gao

et al. 2017

Circulation Research

View full text Add to dashboard Cite

Rationale Platelet hyperreactivity, which is common in many pathological conditions, is associated with increased atherothrombotic risk. The mechanisms leading to platelet hyperreactivity are complex and not yet fully understood. Objective Platelet hyperreactivity and accelerated thrombosis, specifically in dyslipidemia, have been mechanistically linked to accumulation in the circulation of a specific group of oxidized phospholipids (oxPCCD36) that are ligands for the platelet pattern-recognition receptor CD36. In the current manuscript, we tested whether the platelet innate immune system contributes to responses to oxPCCD36 and accelerated thrombosis observed in hyperlipidemia. Methods and Results Using in vitro approaches, as well as platelets from mice with genetic deletion of MyD88 or TLRs, we demonstrate that TLR2 and TLR6 are required for the activation of human and murine platelets by oxPCCD36. oxPCCD36 induce formation of CD36/TLR2/TLR6 complex in platelets and activate downstream signaling via TIRAP-MyD88-IRAK1/4-TRAF6, leading to integrin activation via the SFK-Syk-PLCγ2 pathway. Intravital thrombosis studies using ApoE−/− mice with genetic deficiency of TLR2 or TLR6 have demonstrated that oxPCCD36 contribute to accelerated thrombosis specifically in the setting of hyperlipidemia. Conclusions Our studies reveal that TLR2 plays a key role in platelet hyperreactivity and the prothrombotic state in the setting of hyperlipidemia by sensing a wide range of endogenous lipid-peroxidation ligands and activating innate immune signaling cascade in platelets.

show abstract

Section: Discussionmentioning

confidence: 99%

TLR2 Plays a Key Role in Platelet Hyperreactivity and Accelerated Thrombosis Associated With Hyperlipidemia

Biswas

Zimman

Gao

et al. 2017

Circulation Research

View full text Add to dashboard Cite

show abstract

“…Many phagocytosis receptors play dual roles, including both internalization and adhesion, and these two activities can activate each other [19,20]. Scavenger receptors often function by various mechanisms, including adhesion, phagocytosis, and signaling [51]. A previous study showed that CD36 is essential for LDL-induced macrophage spreading and actin polymerization [28].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Toll-Like Receptor 4 Contributes to Phagocytosis of Salmonella Enterica Serovar Typhimurium via Phosphoinositide 3-Kinase Signaling in Sheep

Wang

Deng

Cao

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Phagocytosis of bacteria by monocytes/macrophages can trigger the immune response and the clearance of bacteria. This innate immune response involves Toll-like receptor 4 (TLR4). However, much remains unknown about the mechanism of TLR4-regulated phagocytosis of Salmonella enterica serovar Typhimurium (S. typhimurium) within sheep monocytes/macrophages. Here, we aimed to address these knowledge gaps by infecting transgenic sheep overexpressing TLR4 with S. typhimurium and examining the phagocytic mechanisms involved. Methods: Transgenic sheep were generated by microinjection of the constructed plasmids into fertilized eggs. Monocytes/macrophages isolated from sheep blood were stimulated with LPS and S. typhimurium. Phagocytosis-related factor expression, phagocytic ability, and adhesion were then determined. TLR4/phosphatidylinositide 3-kinase (PI3K) signaling was inhibited to investigate if this pathway is involved in changes in bacterial internalization in sheep. Results: We found that TLR4 overexpression effectively activated the PI3K signaling pathway and upregulated the expression of scavenger receptors. Additionally, actin polymerization and adhesive capacity were both enhanced in TLR4-overexpressing sheep monocytes/macrophages. TLR4 inhibition decreased S. typhimurium phagocytosis by reducing the actin polymerization and adhesive capacity of cells. Furthermore, inhibition of PI3K markedly impaired TLR4-dependent phagocytosis by restraining actin polymerization and scavenger receptor expression and reduced the adhesive capacity of the monocytes/macrophages. Conclusion: Our findings indicate that overexpression of TLR4 enhances phagocytosis through PI3K signaling and the subsequent activation of actin polymerization and scavenger receptors in sheep monocytes/macrophages infected with S. typhimurium.

show abstract

“…γδ T cells) (Chaplin, 2010; Sonnenberg and Artis, 2015). These effector cells often use pattern recognition molecules such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and scavenger receptors to sense pathogens and danger signals that inititate innate immune responses (Chaplin, 2010; PrabhuDas et al, 2017). Innate immune cells can then release chemokines and cytokines that amplify the immune response by recruiting other immune cells and promoting inter-cellular signaling at the site of injury or infection and distal signaling via the circulatory system.…”

Section: Introductionmentioning

confidence: 99%

“…These molecules interact with receptors such as Toll-like receptors (TLRs) nucleotide-binding oligomerization domain (NOD) like receptors (NLRs) and scavenger receptors that serve as “danger” sensors and help initiate the inflammatory cascade (Jounai et al, 2012; Matzinger, 1994; PrabhuDas et al, 2017). TLR4, which recognizes lipopolysaccharides and multiple endogenous proteins such as high mobility group box 1 protein (HMGB1), heat shock proteins (HSPs), low-density lipoprotein, etc.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

Jassam

Izzy

Whalen

et al. 2017

Neuron

Self Cite

568

496

View full text Add to dashboard Cite

SUMMARY Traumatic brain injury (TBI) is a leading cause of morbidity and disability, with a considerable socioeconomic burden. Heterogeneity of pathoanatomical subtypes and diversity in the pathogenesis and extent of injury contribute to differences in the course and outcome of TBI. Following the primary injury, extensive and lasting damage is sustained through a complex cascade of events referred to as “secondary injury”. Neuroinflammation is proposed as an important manipulable aspect of secondary injury in animal and human studies. Because neuroinflammation can be detrimental or beneficial, before developing immunomodulatory therapies, it is necessary to better understand the timing and complexity of the immune responses that follows TBI. With a rapidly increasing body of literature, there is a need for a clear summary of TBI neuroimmunology. This review presents our current understanding of the immune response to TBI in a chronological and compartment-based manner, highlighting early changes in gene expression and initial signaling pathways that lead to activation of innate and adaptive immunity. Based on recent advances in our understanding of innate immune cell activation, we propose a new paradigm to study innate immune cells following TBI that moves away from the existing M1/M2 classification of activation states towards a stimulus and disease-specific understanding of polarization state based on transcriptomic and proteomic profiling.

show abstract

A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease

Cited by 277 publications

References 168 publications

TLR2 Plays a Key Role in Platelet Hyperreactivity and Accelerated Thrombosis Associated With Hyperlipidemia

TLR2 Plays a Key Role in Platelet Hyperreactivity and Accelerated Thrombosis Associated With Hyperlipidemia

Overexpression of Toll-Like Receptor 4 Contributes to Phagocytosis of Salmonella Enterica Serovar Typhimurium via Phosphoinositide 3-Kinase Signaling in Sheep

Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

Contact Info

Product

Resources

About