RGD Reference Report - IL-27 enhances Leishmania amazonensis infection via ds-RNA dependent kinase (PKR) and IL-10 signaling. - Rat Genome Database

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IL-27 enhances Leishmania amazonensis infection via ds-RNA dependent kinase (PKR) and IL-10 signaling.

Authors: Barreto-de-Souza, Victor  Ferreira, Pedro L C  Vivarini, Aislan de Carvalho  Calegari-Silva, Teresa  Soares, Deivid Costa  Regis, Eduardo G  Pereira, Renata M S  Silva, Aristóbolo M  Saraiva, Elvira M  Lopes, Ulisses G  Bou-Habib, Dumith Chequer 
Citation: Barreto-de-Souza V, etal., Immunobiology. 2015 Apr;220(4):437-44. doi: 10.1016/j.imbio.2014.11.006. Epub 2014 Nov 15.
RGD ID: 126790552
Pubmed: PMID:25466588   (View Abstract at PubMed)
DOI: DOI:10.1016/j.imbio.2014.11.006   (Journal Full-text)

The protozoan parasite Leishmania infects and replicates in macrophages, causing a spectrum of diseases in the human host, varying from cutaneous to visceral clinical forms. It is known that cytokines modulate the immunological response against Leishmania and are relevant for infection resolution. Here, we report that Interleukin (IL)-27 increases Leishmania amazonensis replication in human and murine macrophages and that the blockage of the IL-10 receptor on the surface of infected cells abolished the IL-27-mediated enhancement of Leishmania growth. IL-27 induced the activation/phosphorylation of protein kinase R (PKR) in macrophages, and PKR blockage or PKR gene deletion abrogated the enhancement of the parasite growth driven by IL-27, as well as the L. amazonensis-induced macrophage production of IL-27. We also observed that L. amazonensis-induced expression of IL-27 depends on type I interferon signaling and the engagement of Toll-like receptor 2. Treatment of Leishmania-infected mice with IL-27 increased lesion size and parasite loads in the footpad and lymph nodes of infected animals, indicating that this cytokine exerts a local and a systemic effect on parasite growth and propagation. In conclusion, we show that IL-27 is a L. amazonensis-enhancing factor and that the PKR/IFN1 axis and IL-10 are critical mediators of this IL-27 induced effect.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL27Humanleishmaniasis exacerbatesISOIl27 (Mus musculus) RGD 
Il27Ratleishmaniasis exacerbatesISOIl27 (Mus musculus) RGD 
Il27Mouseleishmaniasis exacerbatesIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il27  (interleukin 27)

Genes (Mus musculus)
Il27  (interleukin 27)

Genes (Homo sapiens)
IL27  (interleukin 27)


Additional Information