Abstract
Polymorphonuclear neutrophils (PMNs) are the first phagocyte recruited and infected by Leishmania. They synthetize superoxide anions (O2−) under the control of the NADPH oxidase complex. In Morocco, Leishmania major and L. tropica are the main species responsible for cutaneous leishmaniasis (CL). The impact of these parasites on human PMN functions is still unclear. We evaluated the in vitro capacity of primary Moroccan strains of L. major and L. tropica to modulate PMN O2− production and p47phox phosphorylation status of the NADPH oxidase complex. PMNs were isolated from healthy blood donors, and their infection rate was measured by microscopy. O2− production was measured by superoxide dismutase–inhibitable reduction of cytochrome C. P47phox phosphorylation was analyzed by Western blot using specific antibodies against Ser328 and Ser345 sites. Whereas we did not observe any difference in PMN infectivity rate, our results indicated that only L. tropica promastigotes inhibited both fMLF- and PMA-mediated O2− production independently of p47phox phosphorylation. Leishmania soluble antigens (SLAs) from both species significantly inhibited O2− induced by fMLF or PMA. However, they only decreased PMA-induced p47phox phosphorylation. L. major and L. tropica modulated differently O2− production by human PMNs independently of p47phox phosphorylation. The inhibition of ROS production by L. tropica could be a mechanism of its survival within PMNs that might explain the reported chronic pathogenicity of L. tropica CL.
Highlights
Nor L. major or L. tropica promastigotes significantly inhibited p47phox phosphorylation on Ser328 (Figure 5B); our results indicate that L. major and L. tropica promastigotes modulated O2 − production induced by fMLF or PMA independently of p47phox phosphorylation
We evaluated whether primary strains of L. major and L. tropica and their respective soluble antigens (SLAs) modulated superoxide anion (O2 − ) production by human polymorphonuclear neutrophils (PMNs) and analyzed the phosphorylation status of the p47phox involved in the activation of the NADPH oxidase [25,30]
To the best of our knowledge, this is the first report addressing the impact of primary moroccan Leishmania species on human PMN activity especially on superoxide anions production
Summary
Leishmania are protozoan parasites causing leishmaniases with 350 million people at risk in about 98 countries or territories, and an incidence of approximately 2 million cases. Previous studies have shown that the clinical manifestations of CL depend as much on the host’s immune response as on the infecting parasite’s virulence factors [5,6,7]. These parasites preferentially infect phagocytic cells, such as macrophages, polymorphonuclear neutrophils (PMNs) and dendritic cells [8]. Following the bite of an infected sandfly, PMNs are the first phagocyte lineage recruited that deliver the parasites to macrophages [9,10,11]. It is likely that PMNs play a dual protective and permissive role shortly after promastigote infection by reducing the incoming parasite burden and subsequently facilitating the safe passage of surviving parasites to naïve host cells [13,14]
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