Immunopathogenesis of infection with the visceralizing Leishmania species

• Published in: Microbial pathogenesis 2005-04, Vol.38 (4), p.147-160
• Main Authors: Wilson, Mary E., Jeronimo, Selma M.B., Pearson, Richard D.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cricetinae; Cytokines - immunology; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Host-Parasite Interactions - immunology; Humans; Leishmania; Leishmania - immunology; Leishmania - pathogenicity; Leishmaniasis, Visceral - immunology; Leishmaniasis, Visceral - parasitology; Mice; Microbiology; Th1 Cells - immunology; Th1 Cells - parasitology; Th2 Cells - immunology; Th2 Cells - parasitology
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2004.11.002

Human leishmaniasis is a spectral disease that includes asymptomatic self-resolving infection, localized skin lesions, and progressive visceral leishmaniasis. With some overlap, visceral and cutaneous leishmaniasis are usually caused by different species of Leishmania. This review focuses on host responses to infection with the species that cause visceral leishmaniasis, as they contrast with species causing localized cutaneous leishmaniasis. Data from experimental models document significant differences between host responses to organisms causing these diverse syndromes. The visceralizing Leishmania spp. cause localized organ-specific immune responses that are important determinants of disease outcome. Both the Leishmania species causing cutaneous and those causing visceral leishmaniasis require a Type 1 immune response to undergo cure in mouse models. However, during progressive murine infection with the visceralizing Leishmania sp., the Type 1 response is suppressed at least in part by TGF-β and IL-10 without type 2 cytokine production. This contrasts with the cutaneous species L. major, in which a Type 2 response suppresses type 1 cytokines and leads to murine disease progression. Population and family studies are beginning to elucidate human genetic determinants predisposing to different outcomes of Leishmania infection. These studies should eventually result in a better understanding of the immunopathogenesis and the spectrum of human leishmaniasis.