RGD Reference Report - STAT-4 mediated IL-12 signaling pathway is critical for the development of protective immunity in cutaneous leishmaniasis. - Rat Genome Database

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STAT-4 mediated IL-12 signaling pathway is critical for the development of protective immunity in cutaneous leishmaniasis.

Authors: Stamm, LM  Satoskar, AA  Ghosh, SK  David, JR  Satoskar, AR 
Citation: Stamm LM, etal., Eur J Immunol. 1999 Aug;29(8):2524-9.
RGD ID: 8661703
Pubmed: PMID:10458767   (View Abstract at PubMed)
DOI: DOI:10.1002/(SICI)1521-4141(199908)29:08<2524::AID-IMMU2524>3.0.CO;2-H   (Journal Full-text)

Recent studies have demonstrated that two IL-12 signaling pathways, a STAT 4 - dependent and STAT4 - independent, are involved in the development of a Th1-like response. To determine their roles in the development of protective immunity against Leishmania major, we monitored progression of cutaneous Leishmania major infection in STAT4-deficient mice (STAT4-/-) compared to similarly infected wild-type (STAT4+/+) mice. Although the onset of lesion growth was delayed in STAT4-/- mice during the early phase of infection, these mice eventually developed large, non-healing lesions, whereas STAT4+/+ mice resolved their lesions. As infection progressed, both STAT4+/+ and STAT4-/- mice infected with L. major displayed similar titers of Leishmania-specific IgG1 and IgE but later produced lower IgG2a. On days 20 and 40 post-infection, Leishmania antigen-stimulated lymphnode cells from STAT4-/- mice produced significantly lower amounts of IFN-gamma than those from STAT4+/+ mice as measured by enzyme-linked immunosorbent assay. There was no significant difference, however, in IL-4 and IL-12 production between the two groups. These results indicate that STAT4-mediated IL-12 signaling is critical for the development of protective Th1 response following L. major infection in genetically resistant mice. Additionally, they demonstrate that, although genetically resistant mice lacking STAT4 signaling pathway develop large, non-healing lesions, they do not default towards a Th2-like response.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
STAT4Humancutaneous leishmaniasis  ISOStat4 (Mus musculus) RGD 
Stat4Ratcutaneous leishmaniasis  ISOStat4 (Mus musculus) RGD 
Stat4Mousecutaneous leishmaniasis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Stat4  (signal transducer and activator of transcription 4)

Genes (Mus musculus)
Stat4  (signal transducer and activator of transcription 4)

Genes (Homo sapiens)
STAT4  (signal transducer and activator of transcription 4)


Additional Information