Intra-specific variability of virulence in Leishmania infantum zymodeme MON-1 strains.
ABSTRACT This study aims to characterize the intra-specific variability of virulence in Leishmania infantum zymodeme MON-1 strains isolated from dogs and immunocompetent and immunosuppressed patients through the evaluation of growth pattern, infective ability and immunopathogenicity. Two of the strains, classified as the most virulent, presented higher levels of macrophage infection, increased promastigote replication in culture medium and as well as amastigote multiplication within macrophages. These strains caused the most pathogenic infection inducing splenomegalia and maximum parasite loads in spleen and liver of BALB/c mice. The other strains exhibited either low virulence, with reduced infective capability and low replication levels, or an intermediate virulent phenotype showing mixed features similar to low and high virulent phenotypes. A correlation between the infectivity, growth dynamics and pathogenicity of each strain and the humoral and cellular immune response was demonstrated. Strains with accentuated virulent phenotype induced higher levels of anti-Leishmania IgG1 antibodies and TGF-beta but reduced production of IFN-gamma. Virulence phenotype seems to be a characteristic of each strain regardless of the host (dog or human) from which it was firstly isolated.
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ABSTRACT: Nitric oxide (NO), the product of the nitric oxide synthase enzymes has been detected in Leishmania-infected animals. Besides its role on the immunity to infection, the role of NO and the inducible nitric oxide synthase (iNOS) in the pathogenesis of canine visceral leishmaniasis (CVL) is not well understood. This study aimed at evaluating immunohistochemically the iNOS expression in the spleen of dogs naturally infected (ID) with Leishmania (L.) chagasi compared with non-infected dogs (NID). The ID was grouped according to the clinical form and the parasite load. Symptomatic dogs (SD) presented higher parasite load in relation to oligosymptomatic (OD) and asymptomatic (AD). The qualitative expression of iNOS was observed only in ID. SD presented strong and prominent labeling of iNOS, followed by OD and AD. Quantitatively, the results showed that the median expression of iNOS was higher in SD and OD compared to NID. Also, dog spleens with high parasitism load showed marked iNOS expression. Taken together, the results suggest that the expression of iNOS in the spleen of infected dogs with CVL was associated with clinical worsening of the disease and with high parasitism.Parasitology Research 12/2010; 108(6):1397-403. · 2.33 Impact Factor
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ABSTRACT: It is well accepted that in experimental model of Leishmania major infection, BALB/c mice mount a Th2 response and produce IgG1 predominantly whereas C57BL/6mice enhance Th1 response with the biased production of IgG2a antibodies. Therefore, screening for parasite antigens on the basis of reactivity with sera from infected susceptible or resistant mice might be used for the identification of Th1- or Th2-inducing antigens.In this study, the antigenic profile of Leishmania majoramastigote that induce IgG1 or IgG2a isotypes in infected BALB/c or C57BL/6 mice were compared.Western blot analyses revealed that 27, 40, 43, 45 and 114 kDa proteins elicited IgG1 and not IgG2a in both BALB/c and C57BL/6 mice and 55 kDa protein was recognized exclusively by IgG1 of BALB/c mice sera. On the contrary, the bands corresponding to proteins with molecular weights (MW) of 30, 35, 52, 58 and 66 were intensively immunostained with IgG2a from C57BL/6 mice which made them potential candidates for eliciting Th1 response.In conclusion, the results showed that the generation of the immune responses depended on the mouse strain and some leishmanial antigens had an intrinsic potency to elicit Th2 responses.Iranian journal of allergy, asthma, and immunology 01/2013; 12(4):361-367. · 1.01 Impact Factor
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ABSTRACT: Visceral Leishmaniasis (VL) caused by species from the Leishmania donovani complex is the most severe form of the disease, lethal if untreated. VL caused by Leishmania infantum is a zoonosis with an increasing number of human cases and millions of dogs infected in the Old and the New World. In this study, L. infantum (syn. L.chagasi) strains were isolated from human and canine VL cases. The strains were obtained from endemic areas from Brazil and Portugal and their genetic polymorphism was ascertained using the LSSP-PCR (Low-Stringency Single Specific Primer PCR) technique for analyzing the kinetoplastid DNA (kDNA) minicircles hypervariable region. KDNA genetic signatures obtained by minicircle LSSP-PCR analysis of forty L. infantum strains allowed the grouping of strains in several clades. Furthermore, LSSP-PCR profiles of L. infantum subpopulations were closely related to the host origin (human or canine). To our knowledge this is the first study which used this technique to compare genetic polymorphisms among strains of L. infantum originated from both the Old and the New World. LSSP-PCR profiles obtained by analysis of L. infantum kDNA hypervariable region of parasites isolated from human cases and infected dogs from Brazil and Portugal exhibited a genetic correlation among isolates originated from the same reservoir, human or canine. However, no association has been detected among the kDNA signatures and the geographical origin of L. infantum strains.PLoS ONE 08/2012; 7(8):e43363. · 3.53 Impact Factor