RGD Reference Report - IL-22 and IDO1 affect immunity and tolerance to murine and human vaginal candidiasis. - Rat Genome Database

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IL-22 and IDO1 affect immunity and tolerance to murine and human vaginal candidiasis.

Authors: De Luca, Antonella  Carvalho, Agostinho  Cunha, Cristina  Iannitti, Rossana G  Pitzurra, Lucia  Giovannini, Gloria  Mencacci, Antonella  Bartolommei, Lorenzo  Moretti, Silvia  Massi-Benedetti, Cristina  Fuchs, Dietmar  De Bernardis, Flavia  Puccetti, Paolo  Romani, Luigina 
Citation: De Luca A, etal., PLoS Pathog. 2013;9(7):e1003486. doi: 10.1371/journal.ppat.1003486. Epub 2013 Jul 11.
RGD ID: 39938863
Pubmed: PMID:23853597   (View Abstract at PubMed)
PMCID: PMC3708875   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.ppat.1003486   (Journal Full-text)

The ability to tolerate Candida albicans, a human commensal of the gastrointestinal tract and vagina, implicates that host defense mechanisms of resistance and tolerance cooperate to limit fungal burden and inflammation at the different body sites. We evaluated resistance and tolerance to the fungus in experimental and human vulvovaginal candidiasis (VVC) as well as in recurrent VVC (RVVC). Resistance and tolerance mechanisms were both activated in murine VVC, involving IL-22 and IL-10-producing regulatory T cells, respectively, with a major contribution by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). IDO1 was responsible for the production of tolerogenic kynurenines, such that replacement therapy with kynurenines restored immunoprotection to VVC. In humans, two functional genetic variants in IL22 and IDO1 genes were found to be associated with heightened resistance to RVVC, and they correlated with increased local expression of IL-22, IDO1 and kynurenines. Thus, IL-22 and IDO1 are crucial in balancing resistance with tolerance to Candida, their deficiencies are risk factors for RVVC, and targeting tolerance via therapeutic kynurenines may benefit patients with RVVC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
vulvovaginal candidiasis  ISOIdo1 (Mus musculus)39938863; 39938863 RGD 
vulvovaginal candidiasis  IMP 39938863 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Recurrent vulvovaginal candidiasis susceptibilityIAGP 39938863DNA:SNP:3'utr: (rs3808606) (human)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ido1  (indoleamine 2,3-dioxygenase 1)

Genes (Mus musculus)
Ido1  (indoleamine 2,3-dioxygenase 1)

Genes (Homo sapiens)
IDO1  (indoleamine 2,3-dioxygenase 1)


Additional Information