title: The site of cutaneous infection influences the immunological response and clinical outcome of hamsters infected with Leishmania panamensis.
abstract: We determined that the site of inoculation (foot or snout) influences the clinical evolution and immune responses of hamsters infected with Leishmania (Viannia) panamensis. Hamsters infected in the snout showed (i) a more rapid and severe lesion evolution at multiple time points (P < 0.05), (ii) a more extensive inflammatory infiltrate and tissue necrosis, (iii) a higher tissue parasite burden, (iv) a higher antibody titre (P < 0.01), but lower antigen-specific spleen cell proliferative response (P = 0.02), and (v) a slower response to anti-leishmanial drug treatment (P < 0.002). In both inoculation groups there was co-expression of type 1 (IFN-gamma and IL-12) and some type 2 (IL-10 and TGF-beta, but not IL-4) cytokines in the cutaneous lesions and spleen. Early in the course of infection, hamsters infected in the snout showed higher expression of splenic IL-10 (P = 0.04) and intra-lesional IFN-gamma (P = 0.02) than foot infections. No expression of IL-12p40 or IL-4 was detected. During the chronic phase, snout lesions expressed more IFN-gamma (P = 0.001), IL-12p40 (P = 0.01), IL-10 (P = 0.009) and TGF-beta (P = 0.001), and the level of expression of each of these cytokines correlated with lesion size (P < or = 0.01). These results suggest that the site of infection influences the clinical outcome in experimental cutaneous leishmaniasis, and that the expression of macrophage-deactivating type 2 cytokines and/or an exaggerated type 1 proinflammatory cytokine response may contribute to lesion severity.
authors.affiliation: Centro Internacional de Entrenamiento e Investigaciones Medicas-CIDEIM, AA5390, Cali, Colombia.
authors.forename: Yaneth
authors.initials: Y
authors.lastname: Osorio
authors.forename: Peter C
authors.initials: PC
authors.lastname: Melby
authors.forename: Claude
authors.initials: C
authors.lastname: Pirmez
authors.forename: Bysani
authors.initials: B
authors.lastname: Chandrasekar
authors.forename: Nora
authors.initials: N
authors.lastname: Guarín
authors.forename: Bruno L
authors.initials: BL
authors.lastname: Travi
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D007370:Interferon Type I / Q000378:metabolism; D018334:Leishmania guyanensis; D007897:Leishmaniasis, Mucocutaneous / Q000276:immunology* / Q000469:parasitology; D012871:Skin Diseases / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D007370:Interferon Type I