Host and parasite roles in the pathogenesis of the leishmaniasis.

by Tarso Gonçalves, Paulo de

Polymorphism in the clinical presentation and evolution of leishmaniasis may depend upon the species of the parasite and the host immune response. The first study showed that peripheral blood mononuclear cells (PBMC) from localizedcutaneous leishmaniasis (LCL) patients stimulated with L. (V.) braziliensis antigenic extracts produced significantly higher IFN-? levels than PBMC from cutaneous disseminated leishmaniasis (DL) patients. In contrast, no difference was noted between the levels of IL-5 and IL-10 in both infections. Antigenic extracts from the L. (V.) braziliensis genotyped isolate from DL patients were more potent in triggering IFN-? and TNF-? levels from LCL and DL patients than the L. (V.) braziliensis genotyped isolate from patients with cutaneous localized leishmaniasis. Such difference was also observed for cutaneous disseminated leishmaniasis antigen triggered production of IL-5 by PBMC of cutaneous leishmaniasis patients but not by PBMC of cutaneous disseminated leishmaniasis patients. In the second study, we evaluated the parasites? response to nitric oxide.The promastigote stage of Leishmania braziliensis and L. (L.) amazonensis parasites, isolated from patients with LCL, ML or LD, were exposed to NaNO2 (nitric oxide donor) and then classified as susceptible or resistant to nitric oxide. Seventeen L. (L.) amazonensis or L. (V.) braziliensis promastigotes were killed by 8 mM or more of NaNO2 (pH 5.0). Nine nitric oxide-resistant isolates survived even in 16 mM NaNO2. Nitric oxide-resistance correlated with disease severity. Patients infected with nitric oxide-resistant Leishmania had significantly larger lesions than patients? nitric oxide-susceptible isolates. In addition, patients with mucocutaneous leishmaniasis were more likely than patients with cutaneous leishmaniasis to have nitric oxide-resistant Leishmania. Lastly, nitric oxide-resistant L. (L.) amazonensis and L. (V.) braziliensis multiplied significantly better in human macrophages and led to the release of significantly lower amounts of nitrite than humanmacrophages infected with nitric oxide-susceptible Leishmania. In the third article, we reviewed key aspects of the immunological response in visceral and Americantegumentary leishmaniasis. Visceral and diffuse cutaneous leishmaniasis patients show negative Montenegro skin tests, indicating a lack of cellular immune response. This imunossupression is antigen specific, as shown in vitro by to a low stimulation index of Leishmania antigen, low IFN-? production ,or high levels of IL-10. Neutralization of IL-10 restores IFN-? production in lymphocytes cultures from these patients. In contrast cutaneous and mucosal leishmaniasis stimulate strong T-cell immunity . The patients present with positive delayed-type hypersensitivity for Leishmania. In vitro studies show intense lymphoproliferative response, production of high levels of IFN-? and necrosis TNF-?. Addition of IL -10 suppressed IFN-? production by 19% in PBMCs cultures from mucosal leishmaniasis patients. Although the control and cure of Leishmania infection depends on a type 1 immune response, the intense inflammatory response observed in cutaneous and mucosal leishmaniasis is involved in their pathogenisis.