Distinct neutrophil effector functions in response to different isolates of Leishmania aethiopica

Abstract Background In Ethiopia, cutaneous leishmaniasis is mainly caused by Leishmania (L.) aethiopica parasites and presents in three main clinical forms. It is still not clear if the host immune response plays a role in the development of these different presentations. Since neutrophils are likel...

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Main Authors: E. Adem, E. Cruz Cervera, E. Yizengaw, Y. Takele, S. Shorter, J. A. Cotton, G. Getti, P. Kropf
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Parasites & Vectors
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Online Access:https://doi.org/10.1186/s13071-024-06489-x
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author E. Adem
E. Cruz Cervera
E. Yizengaw
Y. Takele
S. Shorter
J. A. Cotton
G. Getti
P. Kropf
author_facet E. Adem
E. Cruz Cervera
E. Yizengaw
Y. Takele
S. Shorter
J. A. Cotton
G. Getti
P. Kropf
author_sort E. Adem
collection DOAJ
description Abstract Background In Ethiopia, cutaneous leishmaniasis is mainly caused by Leishmania (L.) aethiopica parasites and presents in three main clinical forms. It is still not clear if the host immune response plays a role in the development of these different presentations. Since neutrophils are likely to be one of the first immune cells present at the site of the sand fly bite, we set up an in vitro model of infection of neutrophils with L. aethiopica and assessed some of the main neutrophil effector functions: association with and internalisation of parasites, apoptosis and ROS production. We used three freshly isolated clinical isolates and one isolate that has been kept in culture for decades. Results Our results showed by flow cytometry that all four L. aethiopica isolates had the ability to associate with neutrophils. The three clinical isolates of L. aethiopica associated more efficiently with neutrophils than the long-term cultured L. aethiopica. At 18 h, two distinct populations of neutrophils were identified that associated with L. aethiopica, CD15high and CD15low neutrophils. Confocal microscopy demonstrated that all isolates can be internalised. Our results also showed that all parasites induced apoptosis in L. aethiopica-associated neutrophils. Moreover, our results showed that after 2 h, L. aethiopica-associated neutrophils upregulated their production of ROS, but to a greater extent with the long-term cultured L. aethiopica. After 18 h of incubation, CD15lowparasite+ showed an impaired ability to produce ROS compared to CD15highparasite+. Conclusions Using this in vitro model, our results show that different L. aethiopica parasite isolates, most notably long-term cultured parasites, had differential effects on neutrophil effector functions. Graphical Abstract
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spelling doaj-art-bd30550e22da41fd90ea036ac23db89c2024-11-17T12:12:38ZengBMCParasites & Vectors1756-33052024-11-0117111310.1186/s13071-024-06489-xDistinct neutrophil effector functions in response to different isolates of Leishmania aethiopicaE. Adem0E. Cruz Cervera1E. Yizengaw2Y. Takele3S. Shorter4J. A. Cotton5G. Getti6P. Kropf7University of GreenwichDepartment of Infectious Disease, Imperial College LondonDepartment of Medical Laboratory Science, College of Medicine and Health Science, Bahir Dar UniversityDepartment of Infectious Disease, Imperial College LondonUniversity of GreenwichSchool of Biodiversity, One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of GlasgowUniversity of GreenwichDepartment of Infectious Disease, Imperial College LondonAbstract Background In Ethiopia, cutaneous leishmaniasis is mainly caused by Leishmania (L.) aethiopica parasites and presents in three main clinical forms. It is still not clear if the host immune response plays a role in the development of these different presentations. Since neutrophils are likely to be one of the first immune cells present at the site of the sand fly bite, we set up an in vitro model of infection of neutrophils with L. aethiopica and assessed some of the main neutrophil effector functions: association with and internalisation of parasites, apoptosis and ROS production. We used three freshly isolated clinical isolates and one isolate that has been kept in culture for decades. Results Our results showed by flow cytometry that all four L. aethiopica isolates had the ability to associate with neutrophils. The three clinical isolates of L. aethiopica associated more efficiently with neutrophils than the long-term cultured L. aethiopica. At 18 h, two distinct populations of neutrophils were identified that associated with L. aethiopica, CD15high and CD15low neutrophils. Confocal microscopy demonstrated that all isolates can be internalised. Our results also showed that all parasites induced apoptosis in L. aethiopica-associated neutrophils. Moreover, our results showed that after 2 h, L. aethiopica-associated neutrophils upregulated their production of ROS, but to a greater extent with the long-term cultured L. aethiopica. After 18 h of incubation, CD15lowparasite+ showed an impaired ability to produce ROS compared to CD15highparasite+. Conclusions Using this in vitro model, our results show that different L. aethiopica parasite isolates, most notably long-term cultured parasites, had differential effects on neutrophil effector functions. Graphical Abstracthttps://doi.org/10.1186/s13071-024-06489-xLeishmania aethiopicaNeutrophilsROSPhagocytosisApoptosis
spellingShingle E. Adem
E. Cruz Cervera
E. Yizengaw
Y. Takele
S. Shorter
J. A. Cotton
G. Getti
P. Kropf
Distinct neutrophil effector functions in response to different isolates of Leishmania aethiopica
Parasites & Vectors
Leishmania aethiopica
Neutrophils
ROS
Phagocytosis
Apoptosis
title Distinct neutrophil effector functions in response to different isolates of Leishmania aethiopica
title_full Distinct neutrophil effector functions in response to different isolates of Leishmania aethiopica
title_fullStr Distinct neutrophil effector functions in response to different isolates of Leishmania aethiopica
title_full_unstemmed Distinct neutrophil effector functions in response to different isolates of Leishmania aethiopica
title_short Distinct neutrophil effector functions in response to different isolates of Leishmania aethiopica
title_sort distinct neutrophil effector functions in response to different isolates of leishmania aethiopica
topic Leishmania aethiopica
Neutrophils
ROS
Phagocytosis
Apoptosis
url https://doi.org/10.1186/s13071-024-06489-x
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