Abstract

BackgroundClinical manifestations of cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) range from asymptomatic infection to self-limited, or chronic (non-healing) cutaneous lesions. Given the critical role of the immune response in the clinical outcome of CL, it is plausible that functional polymorphisms in immune-related genes contribute to define the clinical manifestations of human infection.MethodsDNA samples from a retrospective cohort of individuals from an endemic area of L. V. panamensis transmission in Colombia were used to determine the frequency of SNPs in TNFα, IL-10 and TLR4 genes. DNA samples were obtained from 74 adult participants: 38 patients presenting chronic cutaneous leishmaniasis (CCL) and 36 individuals with asymptomatic infection. Genotyping of TNFα-308G/A, IL-10-819C/T, and TLR4 Asp299Gly and Thr399Ile SNPs, was conducted by PCR-restriction fragment length polymorphisms. Allele, genotype frequencies and associations between SNPs and clinical groups were evaluated.ResultsThe A allele in TNFα-308G/A SNP was found more frequently in individuals with asymptomatic infection (16% vs 7%), whereas the CC genotype in IL-10-819 C/T SNP was more frequent in patients with CCL (34% vs. 27% in asymptomatic individuals). No differences in allele frequencies for TLR4 SNPs were found among groups.ConclusionThis study provides a reference base for statistical power calculation and design of association studies of genetic polymorphisms in immune response related-genes and the pathogenesis of infections caused by L. V. panamensis.

Highlights

  • Clinical manifestations of cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) range from asymptomatic infection to self-limited, or chronic cutaneous lesions

  • Cutaneous leishmaniasis (CL) caused by Leishmania of the Viannia subgenus is characterized by a wide spectrum of clinical manifestations

  • We have previously reported the involvement of TLR4 in TNFα production in human macrophages in response to L.V. panamensis infection, and its participation in the early control of infection [17]

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Summary

Introduction

Clinical manifestations of cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) range from asymptomatic infection to self-limited, or chronic (non-healing) cutaneous lesions. Given the critical role of the immune response in the clinical outcome of CL, it is plausible that functional polymorphisms in immune-related genes contribute to define the clinical manifestations of human infection. Cutaneous leishmaniasis (CL) caused by Leishmania of the Viannia subgenus is characterized by a wide spectrum of clinical manifestations. Polarization of Th1/Th2 responses has been shown to determine resistance and susceptibility in murine models of Leishmania major infection [4, 5]. Correlations between pro- and anti-inflammatory cytokine production and clinical manifestations have been observed. High TNFα production has been shown to contribute to parasite control in early stages of L.

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