Molecular determinants and regulation of Leishmania virulence

A Leishmania model to explain microbial virulence in chronic infectious diseases is proposed. All these diseases progress from infection to symptomatic phase to host death or recovery. The outcome of each phase is depicted to result from the interactions of a distinct group of parasite molecules with a specific host immune compartment. The first group consists of invasive/evasive determinants, which are largely parasite cell surface and secreted molecules. Their activities help parasites establish infection by overcoming host immunologic and non-immunologic barriers. These determinants do not cause disease per se, but are indispensable for infection necessary for the development of a disease-state. The second group of parasite molecules consists of "pathoantigenic" determinants - unique parasite epitopes present often within otherwise highly conserved cytoplasmic molecules. Immune response against these determinants is thought to result in immunopathology manifested as clinical signs or symptoms, namely the virulent phenotype. The third group of parasite molecules is hypothetically perceived as vaccine determinants. Their interactions with the host immune system lead to the elimination or reduction of parasites to effect a clinical cure. Differential expression of these determinants alone by parasites may alter their interactions with the hosts. Virulent phenotype is consequently presented as a spectrum of manifestations from asymptomatic infection to fatality. A secondary level of regulation lies in host genetic and environmental factors. The model suggests that different parasite determinants may be targeted by different strategies to achieve more effective control of leishmaniasis and other similar diseases.