Macrophage MSR1 promotes the formation of foamy macrophage and neuronal apoptosis after spinal cord injury

Kong, Fanqi; Sj, Zhao; Líu, Hao; Jian, Jie; Xu, Tao; Xu, An-Di; Yang, Yaqing; Zhu, Ye; Chen, Jian; Zhou, Zheng; Qian, Dingfei; Gu, Changjiang; Chen, Qi; Yin, Guoyong; Zhang, Hanwen; Fan, Jin

doi:10.1186/s12974-020-01735-2

Cited by 53 publications

(41 citation statements)

References 41 publications

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“…These observations suggest that MSR1 becomes important for VSV infection of the spinal cord at least partly because MSR1 expression is robustly upregulated. On the other hand, MSR1 could contribute to neuronal inflammation and apoptosis by activating NF-κB signaling pathway in the spinal cord (32). However, our data do not necessarily rule out the importance of LDLR family to VSV infection in the spinal cord.…”

Section: Discussioncontrasting

confidence: 68%

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

Yang

Lin

Harrison

et al. 2020

Preprint

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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 ...

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Section: Discussioncontrasting

confidence: 68%

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

Yang

Lin

Harrison

et al. 2020

Preprint

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“…Regarding the intracellular trafficking and vesicular transport pathways, CXCR4 or C-X-C motif chemokine receptor 4 is a gene that is associated specifically to the cytokine-cytokine receptor interaction, leukocyte transendothelial migration and chemokine signaling pathways [40] and is up-regulated in ME. Similarly, MSR1 or macrophage scavenger receptor 1 is related to phagocytosis [41], NKG7 codes for natural killer cell granule protein 7 and is involved in the immune response [42] and CD68 that codes for CD68 molecule protein is associated to the lysosome metabolism. All the genes are therefore involved in the modulation of the inflammatory response.…”

Section: Major Pathways Affected By Weight Loss In the Majorera Mammamentioning

confidence: 99%

Understanding seasonal weight loss tolerance in dairy goats: a transcriptomics approach

et al. 2020

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Background Seasonal weight loss (SWL) is a very important limitation to the production of ruminants in the Mediterranean and Tropical regions. In these areas, long dry seasons lead to poor pastures with low nutritional value. During the dry season, ruminants, particularly those raised in extensive production systems, lose around 30% of their body weight. Seasonal weight loss has important consequences on animal productive performance and health. In this study, RNA sequencing was used to characterize feed restriction effects in dairy goat of 2 breeds with different SWL tolerance: Majorera (tolerant) and Palmera (susceptible). Nine Majorera and ten Palmera goats were randomly distributed in a control and a restricted group: Majorera Control (adequately fed; MC; n = 4), Palmera Control (adequately fed; PC; n = 6), Majorera Restricted (feed restricted; ME; n = 5) and Palmera Restricted (feed restricted; PE; n = 4). On day 22 of the trial, mammary gland biopsies were collected for transcriptomics analysis. Results From these samples, 24,260 unique transcripts were identified. From those, 82 transcripts were differentially expressed between MC and ME, 99 between PC and PE, twelve between both control groups and twenty-nine between both restricted groups. Conclusions Feed restriction affected several biochemical pathways in both breeds such as: carbohydrate and lipid transport; intracellular trafficking, RNA processing and signal transduction. This research also highlights the importance or involvement of the genes in tolerance (ENPP1, S-LZ, MT2A and GPNB) and susceptibility (GPD1, CTPS1, ELOVL6 and NR4A1) to SWL with respectively higher expression in the Majorera restriced group and the Palmera restricted group in comparison to the control groups. In addition, results from the study may be extrapolated to other dairy ruminant species.

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“…These observations suggest that MSR1 is a cofactor facilitating VSV infection in a LDLR family-dependent manner ( Ge et al., 2010 ; Nikolic et al., 2018 ). Additionally, MSR1 could contribute to neuronal inflammation and apoptosis by activating NF-κB signaling pathway in the spinal cord ( Kong et al., 2020 ).…”

Section: Discussionmentioning

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.

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Macrophage MSR1 promotes the formation of foamy macrophage and neuronal apoptosis after spinal cord injury

Cited by 53 publications

References 41 publications

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

Understanding seasonal weight loss tolerance in dairy goats: a transcriptomics approach

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

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