RGD Reference Report - Epidermal Growth Factor Receptor-Responsive Indoleamine 2,3-Dioxygenase Confers Immune Homeostasis During Shigella flexneri Infection. - Rat Genome Database

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

Authors: Mukherjee, Tanushree  Udupa, Vibha A V  Prakhar, Praveen  Chandra, Kasturi  Chakravortty, Dipshikha  Balaji, Kithiganahalli N 
Citation: Mukherjee T, etal., J Infect Dis. 2019 May 5;219(11):1841-1851. doi: 10.1093/infdis/jiz009.
RGD ID: 39938959
Pubmed: PMID:30615126   (View Abstract at PubMed)
DOI: DOI:10.1093/infdis/jiz009   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
muramyl dipeptide increases expression ISOEgf (Mus musculus)39938959; 39938959muramyl dipeptide increases expression of Egf mRNA in splenocytesRGD 
muramyl dipeptide increases expression EXP 39938959muramyl dipeptide increases expression of Egf mRNA in splenocytesRGD 
muramyl dipeptide increases expressionISOIdo1 (Mus musculus)39938959; 39938959muramyl dipeptide increases expression of Ido1 mRNA in peritoneal macrophages and splenocytesRGD 
muramyl dipeptide increases expressionEXP 39938959muramyl dipeptide increases expression of Ido1 mRNA in peritoneal macrophages and splenocytesRGD 

Objects Annotated

Genes (Rattus norvegicus)
Egf  (epidermal growth factor)
Ido1  (indoleamine 2,3-dioxygenase 1)
Il10  (interleukin 10)
Il12b  (interleukin 12B)
Il1b  (interleukin 1 beta)

Genes (Mus musculus)
Egf  (epidermal growth factor)
Ido1  (indoleamine 2,3-dioxygenase 1)
Il10  (interleukin 10)
Il12b  (interleukin 12b)
Il1b  (interleukin 1 beta)

Genes (Homo sapiens)
EGF  (epidermal growth factor)
IDO1  (indoleamine 2,3-dioxygenase 1)
IL10  (interleukin 10)
IL12B  (interleukin 12B)
IL1B  (interleukin 1 beta)


Additional Information