Virulence ofLeishmania infantumIs Expressed as a Clonal and Dominant Phenotype in Experimental Infections

Abstract

Human Leishmania infantum infection results in a spectrum of clinical expressions ranging from cutaneous to either asymptomatic or fatal visceral disease. In this context, characterization of parasite virulence appears to be relevant as a biological marker of intrinsic parasitic factors that can affect the pathology of leishmaniasis. Since parasite populations in naturally infected hosts are likely to be composed of multiclonal associations, we first explored the biodiversity of parasite virulence at the intrastrain level in vitro and in vivo by using 11 clones isolated from three strains previously known to express different virulence phenotypes in mice. Subsequently, we studied the course of infection in mice inoculated simultaneously or successively with strains or clones showing various virulence phenotypes. Analysis of in vitro growth characteristics showed no differences among clones from the different parental strains. By contrast, in vivo experiments evidenced a marked intrastrain heterogeneity of virulence to mice. One out of five clones obtained from a virulent strain showed a typical virulence phenotype, while the remaining four clones had low-virulence profiles, as did the six clones isolated from two low-virulence strains. In mixed multiclonal infections, the virulence phenotype was expressed as a dominant character over the associated low-virulence clones. After a challenge with either a homologous or a heterologous strain or clone, virulence phenotypes were conserved and expressed as in naive mice independently from the preexisting population. These results strongly suggest that parasite virulence in L. infantum visceral leishmaniasis is clonal and dominant in nature.Parasitic infection with Leishmania spp. results in a broad spectrum of clinical diseases in humans. Leishmania infantum is responsible for most cases of human leishmaniasis in southern Europe and reflects this diversity with proteiform clinical expressions ranging from cutaneous leishmaniasis (CL) to either asymptomatic or fatal visceral leishmaniasis (VL).The varying clinical expression observed in VL depends on complex relationships in which not only the genetic potential (3, 4) and/or immunological status of the host (10,15,20) but also the proper parasite biodiversity (15,16,19,26) appear as determinant factors. Characterization of Leishmania polymorphism at the species and subspecies levels is currently based on isoenzyme and biomolecular analysis. However, identification of biological markers like parasite tropism or virulence remains crucial as a complementary tool to account for the considerable biodiversity of the parasite.In this context, characterization of parasite virulence, i.e., the ability to develop and multiply in vitro and/or in vivo appears particularly relevant for analysis of parasitic factors that can affect the pathology of VL. Using 21 Mediterranean strains of L. infantum isolated from humans, we previously showed that there is a remarkable intraspecific heterogeneity in experimental virulence expression of t...

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“…The causative agent of the leishmaniasis, a disease with a wide range of clinical manifestations associated in humans (from selfhealing skin lesions to no less than fatal visceral infection) [1][2][3][4], is made up of unicellular protozoan organisms belonging to the genus Leishmania (L. donovani, L. infantum, L. major, L. tropica, L. aethiopica, L. braziliensis and L. mexicana, among other species [5]) that are transmitted by the bite of infected female sand-flies (Phelobotomus in Europe, Asia and Africa, and Lutzomyia in Americas). [6] Leishmaniasis poses serious public health challenges with regard to its prevention, diagnosis, and treatment [7][8][9].…”

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