Scavenger Receptors: Promiscuous Players during Microbial Pathogenesis

Pombinho, Rita; Sousa, Sandra; Cabanes, Didier

doi:10.1080/1040841x.2018.1493716

Cited by 27 publications

(27 citation statements)

References 150 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, Tim-4 also promoted the phagocytosis of S. aureus (Gram-positive bacteria) and zymosan A, as well as E. coli (Gram-negative bacteria) and Tim-4-mediated phagocytosis of E. coli particles was partially blocked by free LPS (Fig. 4h), suggesting that Tim-4 shows promiscuous ligand binding, which is a general characteristic of scavenger receptors 41 . The identification of further ligands for Tim-4 warrants further study.…”

Section: Discussionmentioning

confidence: 98%

Tim-4 functions as a scavenger receptor for phagocytosis of exogenous particles

et al. 2020

View full text Add to dashboard Cite

The phosphatidylserine (PS) receptor Tim-4 mediates phagocytosis of apoptotic cells by binding to PS exposed on the surface of these cells, and thus functions as a PS receptor for apoptotic cells. Some of PS receptors are capable of recognizing other molecules, such as LPS on bacteria, besides PS on apoptotic cells. However, it is unclear whether Tim-4 perceives other molecules like the PS receptors. Here, we report that Tim-4 facilitates the phagocytosis of exogenous particles as well as apoptotic cells. Similar to the process that occurs during Tim-4-mediated efferocytosis, the uptake of exogenous E. coli and S. aureus bioparticles was promoted by overexpression of Tim-4 on phagocytes, whereas phagocytosis of the bioparticles was reduced in Tim-4-deficient cells. A truncation mutant of Tim-4 lacking the cytoplasmic tail promoted phagocytosis of the particles, but a mutant lacking the IgV or the mucin domain failed to enhance phagocytosis. However, expression of Tim-4AAA (a mutant form of Tim-4 that does not bind phosphatidylserine and does not promote efferocytosis) still promoted phagocytosis. Tim-4-mediated phagocytosis was not blocked by expression of the phosphatidylserine-binding protein Anxa5. Furthermore, binding of lipopolysaccharide (LPS), which is found in the outer membrane of Gram-negative bacteria, was higher in Tim-4-overexpressing cells than in Tim-4-deficient cells. In summary, our study suggests that Tim-4 acts as a scavenger receptor and mediates phagocytosis of exogenous particles in a phosphatidylserine-independent manner.

show abstract

Section: Discussionmentioning

confidence: 98%

Tim-4 functions as a scavenger receptor for phagocytosis of exogenous particles

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Although MSR1 has proven to perform a variety of functions in homeostasis and host immunity due to its ability to recognize a diverse range of ligands (2,3), its role in viral pathogenesis remains poorly defined. MSR1 signaling may be protective against Chikungunya virus and herpes simplex virus infection (11,12), but could also contribute to hepatitis virus-induced liver damage (16).…”

Section: Discussionmentioning

confidence: 99%

“…The above-mentioned data suggest that MSR1 may facilitate VSV infection directly. Of note, MSR1 is known to recognize a wide range of self-and microbial ligands, in particular, oxidized low density lipoproteins (2,3). We thus hypothesized that MSR1 could mediate cellular entry of VSV.…”

Section: Msr1 Mediates Cellular Entry Of Vsvmentioning

confidence: 99%

“…MSR1 recognizes a wide range of ligands including oxidized low-density lipoprotein (oxLDL), endogenous proteins, beta-amyloid, lipoteichoic acid (LTA) and bacterial lipopolysaccharide (LPS) (2,3). The ligand promiscuity of MSR1 is probably due to its function as a component of other pathogen pattern recognition receptor (PRR) signaling complexes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A critical role for MSR1 in vesicular stomatitis virus infection of the central nervous system

Yang

Lin

Harrison

et al. 2020

Preprint

View full text Add to dashboard Cite

21Macrophage scavenger receptor 1 (MSR1) plays an important role in host defense to bacterial 22 infections, M2 macrophage polarization and lipid homeostasis. However, its physiological 23 function in viral pathogenesis remains poorly defined. Herein, we report that MSR1 24 facilitates vesicular stomatitis virus (VSV) infection in the spinal cord. Msr1-deficient 25 (Msr1 -/-) mice presented reduced morbidity and mortality following lethal VSV infection, 26 along with normal viremia and antiviral innate immune responses, compared to Msr1 +/-27 littermates and wild-type mice. Msr1 expression was selectively upregulated in the spinal 28 cord, which was the predominant target of VSV infection. The viral load in the spinal cord 29 was positively correlated with Msr1 expression level and was reduced in Msr1 -/mice.30Through its extracellular domain, MSR1 interacted with VSV surface glycoprotein and 31 facilitated its cellular entry. In conclusion, our results demonstrate that MSR1 serves as a 32 cellular entry receptor for VSV and facilitates its infection specifically in the spinal cord. 33 Key words: vesicular stomatitis virus, MSR1, scavenger receptor. 34 35 36 37 38 39 40 41 3 42 Author Summary 43 As a member of Class A scavenger receptors, macrophage scavenger receptor 1 (MSR1), 44 recognizes various ligands including oxidized low-density lipoproteins (oxLDL), viruses and 45 bacterial lipopolysaccharide (LPS), therefore performs many functions in tissue homeostasis 46 and innate immunity, including pathogen clearance, lipid metabolism, macrophage 47 polarization, and pro-or anti-inflammatory responses in different disease conditions. 48 However, the physiological function of MSR1 during viral infection remains poorly 49 understood. Vesicular stomatitis virus (VSV) is a negative-sense, single-stranded RNA virus, 50 which is common in livestock (e.g. cattle, horses and swine) and produces significant 51 economic losses. VSV is also widely used as an important model virus for fundamental 52 research and vaccine development. But, the mechanism underlying VSV neurotropism is 53 largely unknown. We herein report that MSR1 serves as a cellular receptor facilitating VSV 54 infection specifically in the central nervous system. We demonstrated that MSR1 interacted 55 with VSV virions through its extracellular domain binding to VSV-G protein, and 56 overexpression of the extracellular domain alone was sufficient to promote VSV infection. 57 Our results reveal a novel function for Msr1 as a critical determinant of VSV infection 58 specifically in the spinal cord.59 60 61 62 63 4 64 Introduction 65 Macrophage scavenger receptor 1 (MSR1; also known as CD204, SCARA1 and SR-A1), a 66 member of Class A scavenger receptors, performs many functions in homeostasis and 67 immunity, including pathogen clearance, lipid metabolism and macrophage polarization [1]. 68 MSR1 recognizes a wide range of ligands including oxidized low-density lipoprotein 69 (oxLDL), endogenous proteins, beta-amyloid, lipoteichoic acid (LTA) and bacterial 70 ...

show abstract

“…Macrophage scavenger receptor 1 (MSR1; also known as CD204, SCARA1, and SR-A1), a member of class A scavenger receptors, performs many functions in homeostasis and immunity, including pathogen clearance, lipid metabolism, and macrophage polarization ( Canton et al., 2013 ). MSR1 recognizes a wide range of ligands including oxidized low-density lipoprotein, endogenous proteins, beta-amyloid, lipoteichoic acid (LTA), and bacterial lipopolysaccharide (LPS) ( Pluddemann et al., 2011 ; Pombinho et al., 2018 ). The ligand promiscuity of MSR1 is probably due to its function as a component of other pathogen pattern recognition receptor signaling complexes.…”

Section: Introductionmentioning

confidence: 99%

A critical role for MSR1 in vesicular stomatitis virus infection of the central nervous system

et al. 2021

View full text Add to dashboard Cite

Summary Macrophage scavenger receptor 1 (MSR1) plays an important role in host defense to bacterial infections, M2 macrophage polarization, and lipid homeostasis. However, its physiological function in viral pathogenesis remains poorly defined. Herein, we report that MSR1 facilitates vesicular stomatitis virus (VSV) infection in the central nervous system. Msr1-deficient ( Msr1 −/− ) mice presented reduced morbidity, mortality, and viral loads in the spinal cord following lethal VSV infection, along with normal viremia and innate immune responses, compared to Msr1 +/− littermates and wild-type mice. Msr1 expression was most significantly upregulated in the spinal cord, the predominant target of VSV. Mechanistically, through its extracellular domains, MSR1 interacted with VSV surface glycoprotein and facilitated its cellular entry in a low-density lipoprotein receptor-dependent manner. In conclusion, our results demonstrate that MSR1 serves as a cofactor for VSV cellular entry and facilitates its infection preferentially in the spinal cord.

show abstract

Scavenger Receptors: Promiscuous Players during Microbial Pathogenesis

Cited by 27 publications

References 150 publications

Tim-4 functions as a scavenger receptor for phagocytosis of exogenous particles

Tim-4 functions as a scavenger receptor for phagocytosis of exogenous particles

A critical role for MSR1 in vesicular stomatitis virus infection of the central nervous system

A critical role for MSR1 in vesicular stomatitis virus infection of the central nervous system

Contact Info

Product

Resources

About