Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions
Immunologically, active visceral leishmaniasis (VL) is characterised by profound immunosuppression, severe systemic inflammatory responses and an impaired capacity to control parasite replication. Neutrophils are highly versatile cells, which play a crucial role in the induction as well as the reso...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00517/full |
| _version_ | 1811194576297263104 |
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| author | Endalew Yizengaw Mulusew Getahun Fitsumbrhan Tajebe Edward Cruz Cervera Getnet Mesfin Emebet Adem Asrat Hailu Gert Van der Auwera Vanessa Yardley Mulualem Lemma Ziv Skhedy Ermias Diro Arega Yeshanew Roma Melkamu Bewketu Mengesha Manuel Modolell Markus Munder Ingrid Muller Yegnasew Teferi Pascale Kropf |
| author_facet | Endalew Yizengaw Mulusew Getahun Fitsumbrhan Tajebe Edward Cruz Cervera Getnet Mesfin Emebet Adem Asrat Hailu Gert Van der Auwera Vanessa Yardley Mulualem Lemma Ziv Skhedy Ermias Diro Arega Yeshanew Roma Melkamu Bewketu Mengesha Manuel Modolell Markus Munder Ingrid Muller Yegnasew Teferi Pascale Kropf |
| author_sort | Endalew Yizengaw |
| collection | DOAJ |
| description | Immunologically, active visceral leishmaniasis (VL) is characterised by profound immunosuppression, severe systemic inflammatory responses and an impaired capacity to control parasite replication. Neutrophils are highly versatile cells, which play a crucial role in the induction as well as the resolution of inflammation, the control of pathogen replication and the regulation of immune responses. Neutrophil functions have been investigated in human cutaneous leishmaniasis, however, their role in human visceral leishmaniasis is poorly understood.In the present study we evaluated the activation status and effector functions of neutrophils in patients with active VL and after successful anti-leishmanial treatment. Our results show that neutrophils are highly activated and have degranulated; high levels of arginase, myeloperoxidase and elastase, all contained in neutrophils’ granules, were found in the plasma of VL patients. In addition, we show that a large proportion of these cells are immature. We also analysed effector functions of neutrophils that are essential for pathogen clearance and show that neutrophils have an impaired capacity to release neutrophil extracellular traps, produce reactive oxygen species and phagocytose bacterial particles, but not Leishmania parasites.Our results suggest that impaired effector functions, increased activation and immaturity of neutrophils play a key role in the pathogenesis of VL. |
| first_indexed | 2024-04-12T00:29:30Z |
| format | Article |
| id | doaj.art-0dc483362745420490529fe575be1a0a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T00:29:30Z |
| publishDate | 2016-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0dc483362745420490529fe575be1a0a2022-12-22T03:55:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242016-11-01710.3389/fimmu.2016.00517230902Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functionsEndalew Yizengaw0Mulusew Getahun1Fitsumbrhan Tajebe2Edward Cruz Cervera3Getnet Mesfin4Emebet Adem5Asrat Hailu6Gert Van der Auwera7Vanessa Yardley8Mulualem Lemma9Ziv Skhedy10Ermias Diro11Arega Yeshanew12Roma Melkamu13Bewketu Mengesha14Manuel Modolell15Markus Munder16Ingrid Muller17Yegnasew Teferi18Pascale Kropf19University of GondarUniversity of GondarUniversity of GondarImperial College LondonUniversity of GondarUniversity of GondarUniversity of Addis AbabaInstitute of Tropical MedicineLondon School of Hygiene and Tropical MedicineUniversity of GondarUniversity of HasseltUniversity of GondarUniversity of GondarUniversity of GondarUniversity of GondarMax-Planck-Institute for Immunobiology and EpigeneticsUniversity Medical Center MainzImperial College LondonImperial College LondonImperial College LondonImmunologically, active visceral leishmaniasis (VL) is characterised by profound immunosuppression, severe systemic inflammatory responses and an impaired capacity to control parasite replication. Neutrophils are highly versatile cells, which play a crucial role in the induction as well as the resolution of inflammation, the control of pathogen replication and the regulation of immune responses. Neutrophil functions have been investigated in human cutaneous leishmaniasis, however, their role in human visceral leishmaniasis is poorly understood.In the present study we evaluated the activation status and effector functions of neutrophils in patients with active VL and after successful anti-leishmanial treatment. Our results show that neutrophils are highly activated and have degranulated; high levels of arginase, myeloperoxidase and elastase, all contained in neutrophils’ granules, were found in the plasma of VL patients. In addition, we show that a large proportion of these cells are immature. We also analysed effector functions of neutrophils that are essential for pathogen clearance and show that neutrophils have an impaired capacity to release neutrophil extracellular traps, produce reactive oxygen species and phagocytose bacterial particles, but not Leishmania parasites.Our results suggest that impaired effector functions, increased activation and immaturity of neutrophils play a key role in the pathogenesis of VL.http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00517/fullLeishmaniaNeutrophilsPhagocytosisReactive Oxygen SpeciesVisceral leishmaniasisneutrophil extracellular traps |
| spellingShingle | Endalew Yizengaw Mulusew Getahun Fitsumbrhan Tajebe Edward Cruz Cervera Getnet Mesfin Emebet Adem Asrat Hailu Gert Van der Auwera Vanessa Yardley Mulualem Lemma Ziv Skhedy Ermias Diro Arega Yeshanew Roma Melkamu Bewketu Mengesha Manuel Modolell Markus Munder Ingrid Muller Yegnasew Teferi Pascale Kropf Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions Frontiers in Immunology Leishmania Neutrophils Phagocytosis Reactive Oxygen Species Visceral leishmaniasis neutrophil extracellular traps |
| title | Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions |
| title_full | Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions |
| title_fullStr | Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions |
| title_full_unstemmed | Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions |
| title_short | Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions |
| title_sort | visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions |
| topic | Leishmania Neutrophils Phagocytosis Reactive Oxygen Species Visceral leishmaniasis neutrophil extracellular traps |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00517/full |
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