Scavenger receptor A1 is required for sensing HCMV by endosomal TLR-3/-9 in monocytic THP-1 cells

Yew, Kok-Hooi; Carsten, Bonnie; Harrison, Christopher J.

doi:10.1016/j.molimm.2009.10.009

Cited by 47 publications

(68 citation statements)

References 40 publications

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“…The expression of TLRs in HFF and THP-1 cells has been previously described and these cells were used as reference quality controls (Yew et al 2010).…”

Section: Cell Culturementioning

confidence: 99%

LPS and PAN-induced podocyte injury in an in vitro model of minimal change disease: changes in TLR profile

Srivastava

Sharma

Yew

et al. 2012

J. Cell Commun. Signal.

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Minimal change disease (MCD), the most common idiopathic nephrotic syndrome in children, is characterized by proteinuria and loss of glomerular visceral epithelial cell (podocyte) ultrastructure. Lipopolysaccharide (LPS) and puromycin aminonucleoside (PAN) are used to study podocyte injury in models of MCD in vivo and in vitro. We hypothesized that LPS and PAN influence components of the innate immune system in podocytes such as the Toll-Like Receptor (TLRs), TLR adapter molecules, and associated cytokines. Our results show that cultured human podocytes constitutively express TLRs 1-6 and TLR-10, but not TLRs 7-9. LPS (25 μg/ml) or PAN (60 μg/ml) caused comparable derangement of the actin cytoskeleton in podocytes. Quantitative RT-PCR analysis show that LPS differentially up-regulated the expression of genes for TLRs (1 > 4 ≥ 2 > 3 > 6 > 5), the adapter molecule, MyD88, and transcription factor NF-κB within one hour. LPS also caused increased levels of IL-6, IL-8 and MCP1 without exerting any effect on TNF-α, IFN-α or TGF-β1 at 24 h. Immunofluorescence intensity analysis of confocal microscopy images showed that LPS induced a significant increase in nuclear translocation of NF-κB by 6 h. In contrast, PAN-induced only small changes in the expression of TLRs 2-6 that included a persistent increase in TLRs 2 and 5, a transient increase in TLR-4, and a gradual increase in TLRs 3 and 6 between 1 and 6 h. Correspondingly, it did not alter pro-inflammatory cytokine levels in podocytes. However, PAN induced a low but significant increase in NF-κB nuclear translocation within one hour that remained unchanged up to 6 h. In summary, these novel findings show that LPS, a known TLR-4 ligand, induced the gene expression of multiple TLRs with maximum effect on the expression of TLR-1 suggesting a loss of receptor selectivity and induction of receptor interactions in podocytes. A comparable derangement of the podocyte cytoskeleton and significant increase in the nuclear translocation of NF-κB by PAN suggest that disparate but complementary mechanisms may contribute to the development of podocytopathy in MCD.

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“…The expression of TLRs in HFF and THP-1 cells has been previously described and these cells were used as reference quality controls (Yew et al 2010).…”

Section: Cell Culturementioning

confidence: 99%

LPS and PAN-induced podocyte injury in an in vitro model of minimal change disease: changes in TLR profile

Srivastava

Sharma

Yew

et al. 2012

J. Cell Commun. Signal.

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“…In all these studies, MARCO 2/2 mice showed increased morbidity or mortality because of decreased macrophage-mediated uptake and clearance, leading to exacerbated neutrophil response and enhanced lung pathology. In systemic viral infections, SRA contributes to the uptake and clearance of adenovirus by Kupffer cells (20,21), resistance to herpes virus (22), and human cytomegalovirus recognition by monocytic cells (23). Based on these findings, we initially postulated that the scavenger receptor MARCO would improve host resistance and influenza resolution.…”

mentioning

confidence: 99%

MARCO Regulates Early Inflammatory Responses against Influenza

Ghosh¹,

Gregory²,

Smith³

et al. 2011

Am J Respir Cell Mol Biol

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Lung macrophages use the scavenger receptor MARCO to bind and ingest bacteria, particulate matter, and post cellular debris. We investigated the role of MARCO in influenza A virus (IAV) pneumonia. In contrast to higher susceptibility to bacterial infection, MARCO 2/2 mice had lower morbidity and mortality from influenza pneumonia than wild-type (WT) mice. The early course of influenza in MARCO 2/2 lungs was marked by an enhanced but transient neutrophilic inflammatory response and significantly lower viral replication compared with the WT mice. At later time points, no significant differences in lung histopathology or absolute numbers of T lymphocyte influx were evident. Uptake of IAV by WT and MARCO 2/2 bronchoalveolar lavage macrophages in vitro was similar. By LPS coadministration, we demonstrated that rapid neutrophil and monocyte influx during the onset of influenza suppressed viral replication, indicating a protective role of early inflammation. We hypothesized that the presence of increased basal proinflammatory post cellular debris in the absence of scavenging function lowered the inflammatory response threshold to IAV in MARCO 2/2 mice. Indeed, MARCO 2/2 mice showed increased accumulation of proinflammatory oxidized lipoproteins in the bronchoalveolar lavage early in the infection process, which are the potential mediators of the observed enhanced inflammation. These results indicate that MARCO suppresses a protective early inflammatory response to influenza, which modulates viral clearance and delays recovery.Keywords: inflammation; scavenger receptors; leukocytes; chemokines; pathology; oxidized lipoproteins Influenza is a significant public health concern, being responsible for large numbers of deaths and hospitalizations each year in the United States (1) and worldwide.A successful immune response to influenza balances antiviral mechanisms and the regulation of the inflammation to prevent excessive tissue damage. The early events in the innate immune response often hold the key to such processes (2). After activation by virus, alveolar macrophages (AMs) become highly phagocytic, produce high amounts of inflammatory cytokines such as IL-6 and TNF-a (3), and initiate a cascade of immune responses. AM depletion studies have shown that AMs are indispensable in controlling influenza virus in mice (4) and pigs (5) and in preventing uncontrolled expansion of virus-specific cytotoxic lymphocytes in mouse lungs (6). Activation of macrophage inflammasome pathways by viral RNA is one mechanism linked to decreased morbidity in mouse models (7) and operates in part through recruitment of neutrophils. More generally, neutrophils, which rapidly infiltrate the lung after influenza A virus (IAV) infection, release microbicidal products, such as reactive oxygen species, cationic peptides, eicosanoids, proteolytic enzymes, and elastase (8). Depletion of lung neutrophils in mice, followed by IAV infection, resulted in higher viral titers and increased mortality (9, 10). Mice deficient in mouse chemoattractant protein (...

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“…Recent evidence from our laboratory further indicates that monocytes upon HCMV exposure undergo cellular activation and the induction of pro-inflammatory cytokines, i.e. TNF-α, IFN-β, and IL-12p35, through SR-A1 and TLRs 3 and 9 (Yew et al, 2010).…”

Section: R Domain Interacted With Itself and With S Domain In P3mentioning

confidence: 88%

Development of real-time RT-PCR for human metapneumovirus

Xue¹,

Zheng²,

Zhang³

2011

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Summary. -Literature pertaining to the interactions between Marek΄s disease virus (MDV) entry-related glycoproteins and corresponding receptors is still limited. Results from a Western blot analysis of cellular proteins for virus receptors and co-immunoprecipitation suggest that heat shock protein 70 (HSP70) is a potential cellular receptor for MDV glycoprotein gH. Plaque inhibition assays confirm the involvement of HSP70 in the early stages of MDV entry into chicken embryo fibroblasts (CEF). The present work supports that HSP70 is implicated in the MDV entry process by binding to gH, and enhances the understanding of multifunctional HSP70 and the MDV infection process.

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Scavenger receptor A1 is required for sensing HCMV by endosomal TLR-3/-9 in monocytic THP-1 cells

Cited by 47 publications

References 40 publications

LPS and PAN-induced podocyte injury in an in vitro model of minimal change disease: changes in TLR profile

LPS and PAN-induced podocyte injury in an in vitro model of minimal change disease: changes in TLR profile

MARCO Regulates Early Inflammatory Responses against Influenza

Development of real-time RT-PCR for human metapneumovirus

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