ABSTRACT
Peromyscus yucatanicus (Rodentia: Cricetidae) is a primary reservoir of Leishmania (Leishmania) mexicana (Kinetoplastida: Trypanosomatidae). Nitric oxide (NO) generally plays a crucial role in the containment and elimination of Leishmania. The aim of this study was to determine the amount of NO produced by P. yucatanicus infected with L. (L.) mexicana. Subclinical and clinical infections were established in P. yucatanicus through inoculation with 1 x 10 2 and 2.5 x 10 6 promastigotes, respectively. Peritoneal macrophages were cultured alone or co-cultured with lymphocytes with or without soluble Leishmania antigen. The level of NO production was determined using the Griess reaction. The amount of NO produced was significantly higher (p ≤ 0.0001) in co-cultured macrophages and lymphocytes than in macrophages cultured alone. No differences in NO production were found between P. yucatanicus with subclinical L. (L.) mexicana infections and animals with clinical infections. These results support the hypothesis that the immunological mechanisms of NO production in P. yucatanicus are similar to those described in mouse models of leishmaniasis and, despite NO production, P. yucatanicus is unable to clear the parasite infection.
Subject(s)
Animals , Leishmania mexicana/immunology , Leishmaniasis, Cutaneous/immunology , Macrophages, Peritoneal/parasitology , Nitric Oxide/biosynthesis , Peromyscus/metabolism , Disease Models, Animal , Macrophages, Peritoneal/immunology , Peromyscus/parasitologyABSTRACT
Antecedentes. En el modelo murino más estudiado, producido por L, major, se observa correlación entre cepas resistentes (C57BL6) y susceptibles (BALB/c), con respuestas inmunes Th1 o Th2, respectivamente. Esta dicotomía no se observa en modelos desarrollados con otras especies de Leishmania (L). Por ello es importante avanzar en el estudio de modelos experimentales con especies predominantes de nuestra zona. El objetivo fue reproducir la enfermedad en diferentes cepas murinas luego de la infección por L. amazonensis. Métodos. Para conocer el efecto de la variable cepa de ratones sobre la susceptibilidad a la infección por L. amazonensis, se aplicó un inóculo constante del parásito a las cepas en estudio. Se evaluó la respuesta de las cepas C57BL/6, BALB/c y Swiss, por medición de lesiones, estimación de carga parasitaria e histopatología. Por ELISA se determinaron anticuerpos y citoquinas en suero. Test estadístico: análisis de la varianza (ANOVA). Resultados. BALB/c demostró máxima susceptibilidad a la infección; Swiss presentó un fenotipo intermedio, y C57BL/6 fue la menos susceptible. Se obtuvieron modelos murinos que reprodujeron distintas formas clínicas comparables a la enfermedad humana. Conclusiones. Los resultados servirán para extrapolar a la patología humana las conclusiones de posteriores ensayos terapéuticos y profilácticos sobre animales experimentales.
Background.Most studies have been based onL. majormouse mo-dels, where Th1 and Th2 immune responses are associated with resistant(C57BL/6) and susceptible (BALB/c) strains, respectively. This dichotomyis not generally observed in models developed with otherLeishmania (L.)species. Therefore, the study of mouse models involving species respon-sible for human infections in our region represents an important challen-ge. The aim was to induce the disease in diff erent mouse strains after theinfection withL. amazonensis.Methods.To study the eff ect of mice strain variable over susceptibilityforL. amazonensisinfection, a constant parasite inoculum was appliedto the studied mice strains. Response to infection was characterized inC57BL/6, BALB/c, and Swiss strains by lesion measurement, parasitic loadestimate and histological analysis. Serum presence of antibodies andcytokines was determinated by ELISA. Statistical analysis: ANOVA test.Results.BALB/c showed the maximum level of susceptibility towardsthe infection. Swiss demonstrated an intermediate phenotype andC57BL/6 was the most resistant strain. We could obtain murine modelsrefl ecting diff erent clinical forms present in human disease.Conclusions.These results will be useful to extrapolate to human pa-thology future conclusions about therapeutic and prophylaxis analysison experimental models (Dermatol Argent 2009;15(5):334-339)