Avaliação do papel dos diferentes isolados de Leishmania Braziliensis e dos monócitos na patogênese da Leishmaniose Disseminada

Abstract

Introduction: Disseminated Leishmaniasis (LD) caused by Leishmania braziliensis, is characterized by the presence of 10 or more papular, acneiform and ulcerated lesions. Some studies have shown that L.braziliensis isolated from patients with LD, cutaneous leishmaniasis (CL) and mucosal leishmaniasis (LM) are polymorphic, presenting a genetic diversity that is associated with the clinical forms in American cutaneous leishmaniasis (ATL). Soluble antigen obtained from L.braziliensis isolates from LD patients induces a greater inflammatory response when compared to antigen obtained from isolates from CL patients on cells from CL and LD patients. Studies have shown that monocytes/macrophages from patients with CL and LM behave differently when faced with infection with L.braziliensis when compared to cells from healthy controls (CS). There are still no studies on the behavior of monocytes in LD. Objective: To evaluate the role of monocytes and genotypically different Leishmania braziliensis isolates in the inflammatory response observed in disseminated leishmaniasis. Methods: Monocytes from patients with LD (n=12), LC (n=12) and CS (n=5) were infected with L. braziliensis isolates from patients with LD and isolates from patients with LC in a ratio of 5: 1. Assessment of the degree of infection and parasite load was assessed by counting cytospin preparations by optical microscopy. To analyze the survival of different L. braziliensis isolates in monocytes from patients with LC, LD and CS, viable promastigotes were counted in the culture supernatant using the optical microscopy technique. The evaluation of the production of oxidative radicals was carried out by the oxidation of Dihydrorhodamine 123 (DHR-123) and analyzed using flow cytometry. The expression of TLRs and cytokines/chemokines was evaluated using flow cytometry. Results: The frequency of monocytes from LD patients infected with the LD isolate and the parasite load was higher than that observed in monocytes infected with the LC isolate after 48 hours of infection. The same was observed in cells from patients with CL. The number of viable promastigotes in the supernatant of monocytes infected with the LD isolate was higher when compared with the LC isolate in both groups. The same was observed in CS monocytes. The production of oxidative burst by LD, LC and CS monocytes infected with LD isolate was greater when compared to LC isolate.Conclusion: These results suggest that the genotypic differences of L.braziliensis that causes LD and LC may influence the behavior of this parasite in human monocytes and contribute to the pathogenesis of the disease.