Abstract
BackgroundCutaneous leishmaniasis (CL) is a vector-borne parasitic disease caused by protozoa of the genus Leishmania. In Morocco, CL is a public health problem mainly caused by Leishmania major and Leishmania tropica, which are responsible for zoonotic and anthroponotic CL, respectively. Macrophages are the primary cells infected by Leishmania parasites and their capacity to produce nitric oxide (NO) is of critical importance for parasite elimination. To our knowledge, the role of NO on autochthonous infections has never been investigated before. In this study, we evaluated in vitro the capacity of autochthonous primary dermotropic strains of L. major and L. tropica to modulate NO production by J774-macrophages and determine the sensitivity of both species to exogenous NO.MethodsThe infectivity of the J774 cell line was analyzed by optical microscopy. NO production by macrophages was measured by the Griess method. The sensitivity to NO by the two strains was assessed by the MTT assay using NO donors.ResultsOur results show that the percentage of infected macrophages and the average number of parasites per macrophage were similar for L. major and L. tropica strains. While L. tropica significantly inhibited NO production induced by LPS and IFN-γ stimulation in J774 macrophages, L. major did not affect it. However, soluble Leishmania antigens (SLAs) from both autochthonous primary strains significantly inhibited the production of NO by J774-macrophages in a dose-dependent manner. Finally, our results demonstrated that promastigotes and amastigotes from both strains are sensitive to SNAP NO donor in a dose-dependent manner, although L. tropica demonstrated an increased sensitivity.ConclusionsOur results suggest a differential ability of L. major and L. tropica strains to modulate the capacity of macrophages to produce NO. The increased ability of L. tropica to inhibit NO production by macrophages might come as a necessity due to its higher sensitivity to NO donor. Our results provide one explanation for the tendency of L. tropica to cause chronic lesions and may contribute to the different physiopathology of CL in Morocco.
Highlights
Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease caused by protozoa of the genus Leishmania
Infection of the J774 cell line by L. major and L. tropica primary strains To compare the infectivity of both L. major and L. tropica primary isolates, we employed the well-established J774 cell line as a model for Leishmania infection
Our results indicate that the reduction of nitric oxide (NO) production by L. tropica infected and stimulated macrophages is associated with a significant increase of motile promastigotes produced by these cells
Summary
Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease caused by protozoa of the genus Leishmania. In Morocco, CL is a public health problem mainly caused by Leishmania major and Leishmania tropica, which are responsible for zoonotic and anthroponotic CL, respectively. Leishmaniases are parasitic diseases caused by kinetoplastid protozoans of the family Trypanosomatidae, transmitted by the bite of infected female sand flies belonging to the genera Phlebotomus and Lutzomyia in the Old and New World, respectively [1]. Three main clinical forms of leishmaniasis are reported worldwide: cutaneous leishmaniasis (CL), visceral leishmaniasis (VL) and mucocutaneous leishmaniasis (MCL) They occur in 98 countries and, according to the World Health Organization (WHO), leishmaniasis affects 12 million people worldwide with approximately 0.2–0.4 million VL cases and 0.7–1.2 million CL cases diagnosed each year. In Morocco, CL is a major public health problem, with two main causative entities: the zoonotic form due to Leishmania major and the anthroponotic form due to Leishmania tropica [2]. The promastigotes develop into amastigotes, which multiply inside parasitophorous’ vacuoles in phagocytes [4]
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