ELMO1 has an essential role in the internalization of Salmonella Typhimurium into enteric macrophages that impacts disease outcome

Cellular and Molecular Gastroenterology and Hepatology
Soumita DasPeter B Ernst

Abstract

4-6 million people die of enteric infections each year. After invading intestinal epithelial cells, enteric bacteria encounter phagocytes. However, little is known about how phagocytes internalize the bacteria to generate host responses. Previously, we have shown that BAI1 (Brain Angiogenesis Inhibitor 1) binds and internalizes Gram-negative bacteria through an ELMO1 (Engulfment and cell Motility protein 1)/Rac1-dependent mechanism. Here we delineate the role of ELMO1 in host inflammatory responses following enteric infection. ELMO1-depleted murine macrophage cell lines, intestinal macrophages and ELMO1 deficient mice (total or myeloid-cell specific) was infected with Salmonella enterica serovar Typhimurium. The bacterial load, inflammatory cytokines and histopathology was evaluated in the ileum, cecum and spleen. The ELMO1 dependent host cytokines were detected by a cytokine array. ELMO1 mediated Rac1 activity was measured by pulldown assay. The cytokine array showed reduced release of pro-inflammatory cytokines, including TNF-α and MCP-1, by ELMO1-depleted macrophages. Inhibition of ELMO1 expression in macrophages decreased Rac1 activation (~6 fold) and reduced internalization of Salmonella. ELMO1-dependent internalization wa...Continue Reading

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Citations

Feb 1, 2020·The FEBS Journal·Ibrahim M SayedSoumita Das
Oct 14, 2017·The Journal of Infectious Diseases·Arup SarkarSoumita Das
Oct 16, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lee SwansonPradipta Ghosh

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Methods Mentioned

BETA
nucleotide
GTPase
FACS
pull-down
profiler
enzyme-linked immunosorbent assay
ELISA
transfection
confocal microscopy
GTPases

Software Mentioned

Image Quant
GraphPad

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