The Modulation of NADPH Oxidase Activity in Human Neutrophils by Moroccan Strains of <i>Leishmania major</i> and <i>Leishmania tropica</i> Is Not Associated with p47<sup>phox</sup> Phosphorylation

Polymorphonuclear neutrophils (PMNs) are the first phagocyte recruited and infected by <i>Leishmania</i>. They synthetize superoxide anions (O<sub>2</sub><sup>−</sup>) under the control of the NADPH oxidase complex. In Morocco, <i>Leishmania major</i>...

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Bibliographic Details
Main Authors: Hasnaa Maksouri, Dounia Darif, Jerome Estaquier, Myriam Riyad, Christophe Desterke, Meryem Lemrani, Pham My-Chan Dang, Khadija Akarid
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/9/5/1025
Description
Summary:Polymorphonuclear neutrophils (PMNs) are the first phagocyte recruited and infected by <i>Leishmania</i>. They synthetize superoxide anions (O<sub>2</sub><sup>−</sup>) under the control of the NADPH oxidase complex. In Morocco, <i>Leishmania major</i> and <i>L. tropica</i> 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 <i>L. major</i> and <i>L. tropica</i> to modulate PMN O<sub>2</sub><sup>−</sup> production and p47<sup>phox</sup> phosphorylation status of the NADPH oxidase complex. PMNs were isolated from healthy blood donors, and their infection rate was measured by microscopy. O<sub>2</sub><sup>−</sup> production was measured by superoxide dismutase–inhibitable reduction of cytochrome C. P47<sup>phox</sup> 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 <i>L. tropica</i> promastigotes inhibited both fMLF- and PMA-mediated O<sub>2</sub><sup>−</sup> production independently of p47<sup>phox</sup> phosphorylation. <i>Leishmania</i> soluble antigens (SLAs) from both species significantly inhibited O<sub>2</sub><sup>−</sup> induced by fMLF or PMA. However, they only decreased PMA-induced p47phox phosphorylation. <i>L. major</i> and <i>L. tropica</i> modulated differently O<sub>2</sub><sup>−</sup> production by human PMNs independently of p47<sup>phox</sup> phosphorylation. The inhibition of ROS production by <i>L. tropica</i> could be a mechanism of its survival within PMNs that might explain the reported chronic pathogenicity of <i>L. tropica</i> CL.
ISSN:2076-2607