RGD Reference Report - Interleukin 17A as an effective target for anti-inflammatory and antiparasitic treatment of toxoplasmic uveitis. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Interleukin 17A as an effective target for anti-inflammatory and antiparasitic treatment of toxoplasmic uveitis.

Authors: Sauer, A  Pfaff, AW  Villard, O  Creuzot-Garcher, C  Dalle, F  Chiquet, C  Pelloux, H  Speeg-Schatz, C  Gaucher, D  Prevost, G  Bourcier, T  Candolfi, E 
Citation: Sauer A, etal., J Infect Dis. 2012 Oct;206(8):1319-29. Epub 2012 Aug 22.
RGD ID: 8698652
Pubmed: PMID:22927448   (View Abstract at PubMed)
DOI: DOI:10.1093/infdis/jis486   (Journal Full-text)

BACKGROUND: Toxoplasmosis is the most common cause of posterior uveitis in immunocompetent subjects. The requirement of limiting both parasite multiplication and tissue destruction suggests that the balance between T-helper (Th) 17 and T-regulatory cells is an important factor in toxoplasmosis-induced retinal damage. METHODS: In a prospective clinical study of acute ocular toxoplasmosis, we assessed the cytokine pattern in aqueous humors of 10 affected patients. To determine the immunological mechanisms, we evaluated intraocular inflammation, parasite load, and immunological responses using messenger RNA and protein levels in a mouse model. Anti-interleukin 17A (IL-17A) monoclonal antibodies (mAbs) were administered with the parasite to evaluate the role of IL-17A. RESULTS: Severe ocular inflammation and cytokine patterns comparable to human cases were observed, including IL-17A production. Neutralizing IL-17A decreased intraocular inflammation and parasite load in mice. Detailed studies revealed up-regulation of T-regulatory and Th1 pathways. When interferon gamma (IFN-gamma) was neutralized concomitantly, the parasite multiplication rate was partially restored. CONCLUSIONS: Local IL-17A production by resident cells plays a central role in the pathology of ocular toxoplasmosis. The balance between Th17 and Th1 responses (especially IFN-gamma) is crucial for the outcome of infection. This data reveals new in vivo therapeutic approaches by repressing inflammatory pathways using intravitreal injection of IL-17A mAbs.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL17AHumanOcular Toxoplasmosis treatmentISOIl17a (Mus musculus) RGD 
IL17AHumanOcular Toxoplasmosis  IEP protein:increased expression:aqueous humor (human)RGD 
Il17aRatOcular Toxoplasmosis treatmentISOIl17a (Mus musculus) RGD 
Il17aRatOcular Toxoplasmosis  ISOIL17A (Homo sapiens)protein:increased expression:aqueous humor (human)RGD 
Il17aMouseOcular Toxoplasmosis treatmentIMP  RGD 
Il17aMouseOcular Toxoplasmosis  ISOIL17A (Homo sapiens)protein:increased expression:aqueous humor (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il17a  (interleukin 17A)

Genes (Mus musculus)
Il17a  (interleukin 17A)

Genes (Homo sapiens)
IL17A  (interleukin 17A)


Additional Information