The site of cutaneous infection influences the immunological response and clinical outcome of hamsters infected with Leishmania panamensis.
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.
Osorio
Yaneth
Y
Centro Internacional de Entrenamiento e Investigaciones Medicas-CIDEIM, AA5390, Cali, Colombia.
Melby
Peter C
PC
Pirmez
Claude
C
Chandrasekar
Bysani
B
Guarín
Nora
N
Travi
Bruno L
BL
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*
D000913:Antibodies, Protozoan; D016207:Cytokines; D007370:Interferon Type I