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Epidermal Growth Factor Receptor-Responsive Indoleamine 2,3-Dioxygenase Confers Immune Homeostasis during Shigella flexneri Infection

Mukherjee, T and Udupa, VAV and Prakhar, P and Chandra, K and Chakravortty, D and Balaji, KN (2019) Epidermal Growth Factor Receptor-Responsive Indoleamine 2,3-Dioxygenase Confers Immune Homeostasis during Shigella flexneri Infection. In: Journal of Infectious Diseases, 219 (11). pp. 1841-1851.

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Official URL: https://doi.org/10.1093/infdis/jiz009


The resolution of Shigella flexneri infection-associated hyperinflammation is crucial for host survival. Using in vitro and in vivo models of shigellosis, we found that S. flexneri induces the expression of indoleamine 2,3-dioxygenase 1 (IDO1) through the nucleotide oligomerization domain 2 (NOD2) and epidermal growth factor receptor (EGFR) signaling pathway. Congruently, abrogation of NOD2 or EGFR compromises the ability of S. flexneri to induce IDO1 expression. We observed that the loss of IDO1 function in vivo exacerbates shigellosis by skewing the inflammatory cytokine response, disrupting colon epithelial barrier integrity and consequently limiting the host life-span. Interestingly, administration of recombinant EGF rescued mice from IDO1 inhibition-driven aggravated shigellosis by restoring the cytokine balance and subsequently restricting bacterial growth. This is the first study that underscores the direct implication of the NOD2-EGFR axis in IDO1 production and its crucial homeostatic contributions during shigellosis. Together, these findings reveal EGF as a potential therapeutic intervention for infectious diseases. © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

Item Type: Journal Article
Publication: Journal of Infectious Diseases
Publisher: Oxford University Press
Additional Information: The copyright for this article belongs to Oxford University Press.
Keywords: caspase recruitment domain protein 15; epidermal growth factor receptor; indoleamine 2,3 dioxygenase; cytokine; epidermal growth factor receptor; indoleamine 2,3 dioxygenase, animal cell; animal experiment; animal model; animal tissue; Article; bacterial growth; colon epithelium; controlled study; cytokine response; disease course; enzyme inhibition; enzyme mechanism; immunoregulation; in vitro study; in vivo study; lifespan; mouse; nonhuman; pathogenesis; priority journal; protein expression; protein function; protein synthesis; shigellosis; signal transduction; animal; Bagg albino mouse; genetics; homeostasis; human; immunology; metabolism; microbiology; RAW 264.7 cell line; Shigella flexneri; shigellosis; signal transduction, Animals; Cytokines; Dysentery, Bacillary; ErbB Receptors; Homeostasis; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Mice; Mice, Inbred BALB C; RAW 264.7 Cells; Shigella flexneri; Signal Transduction
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 27 Dec 2022 04:30
Last Modified: 27 Dec 2022 04:30
URI: https://eprints.iisc.ac.in/id/eprint/78549

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