Engulfment and Cell Motility Protein 1 (ELMO1) Has an Essential Role in the Internalization of Salmonella Typhimurium Into Enteric Macrophages That Impact Disease Outcome

Das, Soumita; Sarkar, Arup; Choudhury, Sarmistha Sinha; Owen, Katherine A.; Castillo, Victoria del; Fox, Sarah; Eckmann, Lars; Elliott, Michael R.; Casanova, James E.; Ernst, Peter B.

doi:10.1016/j.jcmgh.2015.02.003

Cited by 35 publications

(98 citation statements)

References 30 publications

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“…Control and ELMO1 small-hairpin RNA (shRNA) macrophage (J774) cells were maintained in high glucose Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal calf serum, as described previously 15 . THP-1 cells were maintained in RPMI media containing 10 mM HEPES, 10 % FBS at a cell concentration of lower than 10 6 cells/ml 19 .…”

Section: Cell Lines and Cell Culturementioning

confidence: 99%

“…Approximately 2x10 5 cells were plated onto a 0.4 µm pore transwell insert and infected with bacteria with moi 10. Bacterial internalization was determined after 6 h of infection of WT and ELMO1-/-EDMs with AIEC-LF82 by gentamicin protection assay 15,18 .…”

Section: Bacterial Internalization By Gentamicin Protection Assaymentioning

confidence: 99%

“…We recently demonstrated that Engulfment and cell motility protein 1 (ELMO1) is a microbial sensor that enables macrophages to engulf enteric bacteria, and coordinately mount inflammation while orchestrating bacterial clearance via the phagolysosomal pathway [15][16][17] .…”

Section: Introductionmentioning

confidence: 99%

“…ELMO1 binds the Pattern Recognition Receptor (PRR) Brain Angiogenesis Inhibitor-1 (BAI1) which recognizes bacterial Lipopolysaccharide (LPS) 18 . BAI1-ELMO1 signaling axis activates Rac1 and induces pro-inflammatory cytokines Tumor necrosis factor-TNF-and Monocyte Chemoattractant protein 1 (MCP-1) 15,19 . BAI1-ELMO1 signaling axis regulates the expression of ATP-binding cassette transporter ABCA1 which is linked to the development of cardiovascular diseases (CVD) 20 .…”

Section: Introductionmentioning

confidence: 99%

“…Genome wide association studies (GWAS) have revealed the association of single nucleotide polymorphisms (SNPs) in ELMO1 with IBD, rheumatoid arthritis (RA) kidney disease and diabetic nephropathy [21][22][23] . ELMO1 is required for the induction of several proinflammatory cytokines that are known to drive a plethora of inflammatory diseases including IBD, CVD and RA 15 . Among them, MCP-1 is a chemokine, which plays a significant role in the recruitment of mononuclear cells to the site of inflammation; it is also one of the major cytokines involved in inflammatory diseases like IBD 24 .…”

Section: Introductionmentioning

confidence: 99%

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Dysregulation of the engulfment pathway in the gut fuels Inflammatory Bowel Disease

Suarez

Lim

Singh

et al. 2018

Preprint

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BACKGROUND & AIMSLuminal dysbiosis is ubiquitous in inflammatory bowel disease (IBD), but how the microbes trigger pro-inflammatory cascades in the epithelial and phagocytic cells remains unknown. Here we investigated the role of the microbial sensor ELMO1 (Engulfment and Cell Motility Protein-1) in sensing and responding to IBD-associated microbes in the gut epithelium and in macrophages.METHODSA stem cell-based technique is used to grow enteroids from WT and ELMO1−/−mice and from colonic biopsies of patients with IBD and subsequently differentiate them into enteroid-derived monolayers (EDMs) that mimic the gut epithelium/Gut in a dish. EDMs infected with IBD-associated invasive E. coli-LF82 were analyzed for bacterial internalization, cytokine production and monocyte-recruitment when co-cultured with monocytes.RESULTSExpression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria in IBD, higher expression correlated with elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. ELMO1-/-murine EDMs displayed a significant reduction of bacterial internalization through epithelial tight junctions and in MCP-1 production compared to WT mice. MCP-1 that is released from the epithelium recruited monocytes. Once recruited, macrophages required ELMO1 to engulf the bacteria and propagate a robust pro-inflammatory cytokine storm (TNF-α).CONCLUSIONSELMO1 couples microbial-sensing to inflammation in both phagocytic and non-phagocytic host cells; it is required for the production of MCP-1 in the epithelium and TNF-α in macrophages. Findings raise the possibility that upregulation of epithelial ELMO1 and the epithelial ELMO1→MCP-1 axis may serve as an early biomarker and therapeutic target, respectively, in IBD and other disorders of inflammation.

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Section: Cell Lines and Cell Culturementioning

confidence: 99%

Section: Bacterial Internalization By Gentamicin Protection Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dysregulation of the engulfment pathway in the gut fuels Inflammatory Bowel Disease

Suarez

Lim

Singh

et al. 2018

Preprint

Self Cite

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Phagocytosis by macrophages depends on histamine H2 receptor signaling and scavenger receptor 1

et al. 2019

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The histamine H2 receptor (H2R) is a G protein‐coupled receptor that mediates cyclic AMP production, protein kinase A activation, and MAP kinase signaling. In order to explore the multifaceted effects of histamine signaling on immune cells, phagocytosis was evaluated using primary mouse‐derived macrophages. Phagocytosis is initiated by signaling via surface‐bound scavenger receptors and can be regulated by autophagy. Absence of H2R signaling resulted in diminished phagocytosis of live bacteria and synthetic microspheres by primary macrophages from histamine H2 receptor gene (Hrh2)‐deficient mice. Flow cytometry and immunofluorescence microscopy were used to quantify phagocytosis of phylogenetically diverse bacteria as well as microspheres of defined chemical composition. Autophagy and scavenger receptor gene expression were quantified in macrophages after exposure to Escherichia coli. Expression of the autophagy genes, Becn1 and Atg12, was increased in Hrh2 −/− macrophages, indicating upregulation of autophagy pathways. Expression of the Macrophage Scavenger Receptor 1 gene (Msr1) was diminished in Hrh2‐deficient macrophages, supporting the possible importance of histamine signaling in scavenger receptor abundance and macrophage function. Flow cytometry confirmed diminished MSR1 surface abundance in Hrh2 −/− macrophages. These data suggest that H2R signaling is required for effective phagocytosis by regulating the process of autophagy and scavenger receptor MSR1 abundance in macrophages.

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Insights into cryptic diversity and adaptive evolution of the clam Coelomactra antiquata (Spengler, 1802) from comparative transcriptomics

et al. 2019

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Engulfment and Cell Motility Protein 1 (ELMO1) Has an Essential Role in the Internalization of Salmonella Typhimurium Into Enteric Macrophages That Impact Disease Outcome

Cited by 35 publications

References 30 publications

Dysregulation of the engulfment pathway in the gut fuels Inflammatory Bowel Disease

Dysregulation of the engulfment pathway in the gut fuels Inflammatory Bowel Disease

Phagocytosis by macrophages depends on histamine H2 receptor signaling and scavenger receptor 1

Insights into cryptic diversity and adaptive evolution of the clam Coelomactra antiquata (Spengler, 1802) from comparative transcriptomics

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