Abstract
Leishmania (Viannia) species are the major agents of cutaneous leishmaniasis (CL) in the Americas. Ulcerative stigmatizing skin lesions generally characterize CL. The microenvironment during Leishmania infection is rich in inflammatory cells and molecules, which contrasts with low oxygen levels. The hypoxia-inducible factor (HIF)-1α activates several genes in response to hypoxia and inflammatory reactions, but its role in the CL course is poorly understood. We investigated the expression pattern of the genes HIF-1α, arginase, inducible NO synthase (iNOS), interferon (IFN)-γ, interleukin (IL)-12, and IL-10 in skin lesions and lymph nodes of golden hamsters infected with L. braziliensis, L. lainsoni, and L. naiffi. The animals were infected and followed for 105 days, with paw volume measurements and photos taken weekly. Euthanasia was performed at 0, 15, 56, and 105 days post-infection. The parasite load of paw and lymph node tissues were measured through absolute quantification at real-time PCR (qPCR), and reverse transcription qPCR (RT-qPCR) was applied to demonstrate the relative mRNA expression of the target genes. Among groups, animals infected with L. braziliensis had the highest parasite load in paws and lymph nodes. HIF-1α mRNA was down-regulated during chronic Leishmania (Viannia) infection but demonstrated less inhibition in hamsters infected with L. lainsoni and L. naiffi. Arginase was the most detectable gene in animals infected by L. braziliensis; IFN-γ and IL-10 genes were the most detectable in L. lainsoni and L. naiffi-infected animals. HIF-1α gene transcription seemed to be down-modulated byL. (Viannia)infection and was less inhibited by L. lainsoni and L. naiffi when compared toL. braziliensis. Animals with L. lainsoni and L. naiffi showed better control of the disease. Further studies are necessary to evaluate the mechanism influencing HIF-1α expression and its role on CL protection; such research could elucidate potential use of HIF-1α as a therapeutic target.
Published Version
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