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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MDPI AG
2021-05-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/5/1025 |
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| author | Hasnaa Maksouri Dounia Darif Jerome Estaquier Myriam Riyad Christophe Desterke Meryem Lemrani Pham My-Chan Dang Khadija Akarid |
| author_facet | Hasnaa Maksouri Dounia Darif Jerome Estaquier Myriam Riyad Christophe Desterke Meryem Lemrani Pham My-Chan Dang Khadija Akarid |
| author_sort | Hasnaa Maksouri |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T11:34:09Z |
| format | Article |
| id | doaj.art-e4901649f38d45339cf187f8f0437d79 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T11:34:09Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-e4901649f38d45339cf187f8f0437d792023-11-21T19:02:01ZengMDPI AGMicroorganisms2076-26072021-05-0195102510.3390/microorganisms9051025The 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> PhosphorylationHasnaa Maksouri0Dounia Darif1Jerome Estaquier2Myriam Riyad3Christophe Desterke4Meryem Lemrani5Pham My-Chan Dang6Khadija Akarid7Research Team on Immunopathology of Infectious and Systemic Diseases, Laboratory of Cellular and Molecular Pathology, Faculty of Medicine and Pharmacy (FMPC), Hassan II University of Casablanca (UH2C), 20000 Casablanca, MoroccoMolecular Genetics and Immunophysiopathology Research Team, Health and Environment Laboratory, Aïn Chock Faculty of Sciences, UH2C, 20000 Casablanca, MoroccoINSERM U1124, Paris University, 75006 Paris, FranceResearch Team on Immunopathology of Infectious and Systemic Diseases, Laboratory of Cellular and Molecular Pathology, Faculty of Medicine and Pharmacy (FMPC), Hassan II University of Casablanca (UH2C), 20000 Casablanca, MoroccoFaculty of Medicine of the Kremlin-Bicêtre, University Paris-Sud, 94270 Paris, FranceLaboratory of Parasitology and Vector-Borne-Diseases, Institut Pasteur du Maroc, 20250 Casablanca, MoroccoINSERM-U1149, CNRS-ERL8252, Inflammation Research Center, 75018 Paris, FranceMolecular Genetics and Immunophysiopathology Research Team, Health and Environment Laboratory, Aïn Chock Faculty of Sciences, UH2C, 20000 Casablanca, MoroccoPolymorphonuclear 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.https://www.mdpi.com/2076-2607/9/5/1025<i>Leishmania</i>neutrophilsNADPH oxidaseROSp47<sup>phox</sup> |
| spellingShingle | Hasnaa Maksouri Dounia Darif Jerome Estaquier Myriam Riyad Christophe Desterke Meryem Lemrani Pham My-Chan Dang Khadija Akarid 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 Microorganisms <i>Leishmania</i> neutrophils NADPH oxidase ROS p47<sup>phox</sup> |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | <i>Leishmania</i> neutrophils NADPH oxidase ROS p47<sup>phox</sup> |
| url | https://www.mdpi.com/2076-2607/9/5/1025 |
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