Does the Leishmania major paradigm of pathogenesis and protection hold for New World cutaneous leishmaniases or the visceral disease?
Parasitic protozoa of the genus Leishmania have provided a useful perspective for immunologists in terms of host defense mechanisms critical for the resolution of infection caused by intracellular pathogens. These organisms, which normally reside in a late endosomal, major histocompatibility complex (MHC) class II(+) compartment within host macrophages cells, require CD4(+) T-cell responses for the control of disease. The paradigm for the CD4(+) T-helper 1 (Th1)/Th2 dichotomy is largely based on the curing/non-curing responses, respectively, to Leishmania major infection. However, this genus of parasitic protozoa is evolutionarily diverse, with the cutaneous disease-causing organisms of the Old World (L. major) and New World (Leishmania mexicana/ Leishmania amazonensis) having diverged 40-80 million years ago. Further adaptations to survive within the visceral organs (for Leishmania donovani, Leishmania chagasi, and Leishmania infantum) must have been required. Consequently, significant differences in host-parasite interactions have evolved. Different virulence factors have been identified for distinct Leishmania species, and there are profound differences in the immune mechanisms that mediate susceptibility/resistance to infection and in the pathology associated with disease. These variations not only point to interesting features of the host-pathogen interaction and immunobiology of this genus of parasitic protozoa, but also have important implications for immunotherapy and vaccine development.
McMahon-Pratt
Diane
D
Department of Epidemiology & Public Health, Yale University School of Medicine, New Haven, CT, USA. diane.mcmahon-pratt@yale.edu
Alexander
James
J
D000818:Animals; D019143:Evolution, Molecular; D006790:Host-Parasite Interactions; D006801:Humans; D007891:Leishmania / Q000145:classification* / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D018320:Leishmania major / Q000145:classification* / Q000276:immunology / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology; D051379:Mice; D008815:Mice, Inbred Strains; D014774:Virulence