Different Leishmania species determine distinct profiles of immune and histopathological responses in CBA mice

Most experimental studies on leishmaniasis compare two different inbred str ains of mice that are resistant or susceptible to one species of Leishmania . In the present study we characterized some cytokines and nitric oxide pro duction as well as histological changes related to resistance and susceptib ility in isogenic CBA mice infected with Leishmania major or Leishmania ama zonensis. CBA mice are capable of controlling infection with L. major, but they succumb to infection with L, amazonensis. Cells from susceptible L. am azonensis-infected CBA mice produced interleukin (IL)-4 and IL-10 but no in terferon (IFN)-gamma. On the other hand, resistant L. major-infected CBA mi ce produced IFN-gamma and IL-10, but IL-4 was detected only in the first we ek of infection. Histopathological studies showed patterns of tissue respon ses at the site of the infection and in the draining lymph nodes that corre lated with resistance or susceptibility. Resistant mice showed a mixed infl ammatory cell infiltration and granulomas in the lesions, whereas in suscep tible mice only heavily parasitized macrophages were seen. Our results indi cate an important role of the parasite species in determining the pattern o f immune response. L. amazonensis induces a Th2-type immune response, where as L. major induces a Th1-type response. These factors must be identified a nd taken into account in the strategies for the development of vaccines aga inst leishmaniasis. The model presented here will be useful for the study o f such factors. (C) 2000 Editions scientifiques et medicales Elsevier SAS.