Heterogeneity of wild Leishmania major isolates in experimental murine pathogenicity and specific immune response

Virulence variability was investigated by analyzing the experimental pathog enicity of 19 Leishmania major strains in susceptible BALB/c mice. Twelve s trains were isolated from Tunisian patients with zoonotic cutaneous leishma niasis; seven strains were isolated in Syria (n = 1), Saudi Arabia (n = 2), Jordan (n = 2), or Israel (n = 2). BALB/c mice were injected in the hind f ootpad with 2 x 10(6) amastigotes of the various isolates, and lesion progr ession was recorded weekly for 9 weeks. Interleukin-4 (IL-4) and gamma inte rferon (IFN-gamma) production of lymph node mononuclear cells activated in vitro with parasite antigens were evaluated 5 weeks after infection. We sho w that disease progression induced by different L. major isolates was large ly heterogeneous although reproducible results were obtained when using the same isolate. Interestingly, isolates from the Middle East induced a more severe disease than did the majority of Tunisian isolates. Strains with the highest virulence tend to generate more IL-4 and less IFN-gamma in vitro a t week 5 postinfection as well as higher levels of early IL-4 mRNA in the l ymph node draining the inoculation site at 16 h postinfection. These result s suggest that L. major isolates from the field may differ in virulence, wh ich influences the course of the disease induced in mice and the type of im mune response elicited by the infected host.