Comparative Immunology, Microbiology & Infectious Diseases 30 (2007) 41–53 Intra-specific variability of virulence in Leishmania infantum zymodeme MON-1 strains Teresa Baptista-Fernandes, Cla´udia Marques, Olivia Roos Rodrigues, Gabriela Maria Santos-Gomes à Unidadede Leishmanioses, Centro de Mala´ria e outras Doenc - as Tropicais, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa, Rua da Junqueira 96, 1349-008 Lisboa, Portugal Accepted 2 October 2006 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-b but reduced production of IFN-g. Virulence phenotype seems to be a characteristic of each strain regardless of the host (dog or human) from which it was firstly isolated. r 2006 Elsevier Ltd. All rights reserved. Keywords: L. infantum; Virulence; Murine model; Immunopathogenesis; IgG1; IgG2a; TGF-b; IFN-g ARTICLE IN PRESS www.elsevier.com/locate/cimid 0147-9571/$ - see front matter r 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.cimid.2006.10.001 à Corresponding author. Tel.: +351 21 3652600; fax: +351 21 3622458/3632105. E-mail address: santosgomes@ihmt.unl.pt (G.M. Santos-Gomes).