Characterization of the biology and infectivity of Leishmania infantum viscerotropic and dermotropic strains isolated from HIV plus and HIV- patients in the murine model of visceral leishmaniasis

被引:37
作者
Cunha, Joana [1 ,2 ,3 ]
Carrillo, Eugenia [4 ]
Sanchez, Carmen [4 ]
Cruz, Israel [4 ]
Moreno, Javier [4 ]
Cordeiro-da-Silva, Anabela [1 ,5 ]
机构
[1] Univ Porto, IBMC Inst Biol Mol & Celular, Unit Infect & Immun, Parasite Dis Grp, P-4150180 Porto, Portugal
[2] Univ Porto, Inst Ciencias Biomed Abel Salazar, P-4150180 Porto, Portugal
[3] Univ Porto, Fac Med, P-4150180 Porto, Portugal
[4] Inst Salud Carlos III, Ctr Nacl Microbiol, WHO Collaborating Ctr Leishmaniasis, Madrid, Spain
[5] Univ Porto, Fac Farm, Dept Ciencias Biol, Microbiol Lab, P-4150180 Porto, Portugal
关键词
Leishmania infantum; Clinical isolates; Visceral leishmaniasis; Molecular typing; Metacyclogenesis; Infectivity; Tropism; IMMUNE-RESPONSE; CANINE LEISHMANIASIS; DONOVANI COMPLEX; MAJOR INFECTION; VIRULENCE; EXPRESSION; PARASITE; GENE; DIAGNOSIS; STAGE;
D O I
10.1186/1756-3305-6-122
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
Background: Leishmaniasis is a group of diseases with a variety of clinical manifestations. The form of the disease is highly dependent on the infective Leishmania species and the immunological status of the host. The infectivity of the parasite strain also plays an important role in the progression of the infection. The aim of this work is to understand the influence of the natural infectivity of Leishmania strains in the outcome of visceral leishmaniasis. Methods: In this study we have characterized four strains of L. infantum in terms of molecular typing, in vitro cultivation and differentiation. Two strains were isolated from HIV+ patients with visceral leishmaniasis (Bibiano and E390M), one strain was isolated from a cutaneous lesion in an immunocompetent patient (HL) and another internal reference strain causative of visceral leishmaniasis (ST) also from an immunocompetent patient was used for comparison. For this objective, we have compared their virulence by in vitro and in vivo infectivity in a murine model of visceral leishmaniasis. Results: Molecular typing unraveled a new k26 sequence attributed to MON-284 zymodeme and allowed the generation of a molecular signature for the identification of each strain. In vitro cultivation enabled the production of promastigotes with comparable growth curves and metacyclogenesis development. The HL strain was the most infective, showing the highest parasite loads in vitro that were corroborated with the in vivo assays, 6 weeks post-infection in BALB/c mice. The two strains isolated from HIV+ patients, both belonging to two different zymodemes, revealed different kinetics of infection. Conclusion: Differences in in vitro and in vivo infectivity found in the murine model were then attributed to intrinsic characteristics of each strain. This work is supported by other studies that present the parasite's inherent features as factors for the multiplicity of clinical manifestations and severity of leishmaniasis.
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