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2016-03-31
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- IOC - Artigos de Periódicos [12967]
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IL-27 ENHANCES LEISHMANIA AMAZONENSIS INFECTION VIA DS-RNADEPENDENT KINASE (PKR) AND IL-10 SIGNALING
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Abstract
tThe protozoan parasite Leishmania infects and replicates in macrophages, causing a spectrum of diseasesin the human host, varying from cutaneous to visceral clinical forms. It is known that cytokines modulatethe immunological response against Leishmania and are relevant for infection resolution. Here, we reportthat Interleukin (IL)-27 increases Leishmania amazonensis replication in human and murine macrophagesand that the blockage of the IL-10 receptor on the surface of infected cells abolished the IL-27-mediatedenhancement 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 parasitegrowth driven by IL-27, as well as the L. amazonensis-induced macrophage production of IL-27. We alsoobserved that L. amazonensis-induced expression of IL-27 depends on type I interferon signaling and theengagement of Toll-like receptor 2. Treatment of Leishmania-infected mice with IL-27 increased lesionsize and parasite loads in the footpad and lymph nodes of infected animals, indicating that this cytokineexerts a local and a systemic effect on parasite growth and propagation. In conclusion, we show thatIL-27 is a L. amazonensis-enhancing factor and that the PKR/IFN1 axis and IL-10 are critical mediators ofthis IL-27 induced effect.
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