Oxidative Stress and Survival of Leishmania spp.: A Relationship of Inverse Proportionality for Disease Outcome

Abstract The development of oxidative stress depends on the deregulation of the fine balance between the proportion of reactive oxygen species (ROS) generation and the activity of antioxidants. As oxidative stress is deleterious for Leishmania sp., their host cell generates ROS as one of the foremo...

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Main Authors: Souravi Roy, Mayumi Mandal, Moumita Halder, Pijush K. Das, Anindita Ukil
Format: Article
Language:English
Published: Cambridge University Press 2025-01-01
Series:Expert Reviews in Molecular Medicine
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Online Access:https://www.cambridge.org/core/product/identifier/S1462399425100100/type/journal_article
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author Souravi Roy
Mayumi Mandal
Moumita Halder
Pijush K. Das
Anindita Ukil
author_facet Souravi Roy
Mayumi Mandal
Moumita Halder
Pijush K. Das
Anindita Ukil
author_sort Souravi Roy
collection DOAJ
description Abstract The development of oxidative stress depends on the deregulation of the fine balance between the proportion of reactive oxygen species (ROS) generation and the activity of antioxidants. As oxidative stress is deleterious for Leishmania sp., their host cell generates ROS as one of the foremost defence strategies. The parasites have also raised a variety of counteracting tricks in order to conquer this challenge. Upon infection, the host’s own antioxidant system is activated by the parasite to neutralise the oxidative stress-mediated protection. In addition to using the host’s antioxidant mechanisms, some genes within the parasite also make them more tolerant against oxidative stress. Therefore, the present review focuses on some major regulators intimately related to the equilibrium between oxidation and antioxidation following infection with Leishmania sp., which may be helpful in developing a comprehensive knowledge of this specific wing of infection biology associated with oxidative stress. Search Results Reactive oxygen species (ROS) play a dual role in leishmaniasis by contributing to both host defence and parasite survival mechanisms. In the host, ROS promote parasite clearance through induction of apoptosis, activation of pro-inflammatory signalling pathways (e.g., MAPK, JNK), inflammasome assembly, and M1 macrophage polarisation. Conversely, Leishmania species have evolved multiple strategies to neutralize ROS, including the upregulation of host antioxidant enzymes like HO-1, inhibition of ROS-producing pathways, and expression of parasite-derived antioxidants such as SOD, GPx, and trypanothione reductase. The parasite alsoadapts through gene regulation and metabolic changes to counter oxidative stress. Importantly, ROS have emerged as key targets for antileishmanial therapies, with various drugs and natural compounds shown to induce ROS-mediated parasite death, highlighting their potential in future therapeutic development. Conclusions In summary, the survival of Leishmania hinges on its ability to counteract host-induced oxidative stress. Targeting its antioxidant defences and enhancing host ROS production can disrupt this balance, leading to parasite death. Exploring ROS-related signalling offers a promising path for developing effective therapies against leishmaniasis.
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spelling doaj-art-cb785143a1394a4da2b96fc9cbd412182025-08-20T12:57:28ZengCambridge University PressExpert Reviews in Molecular Medicine1462-39942025-01-012710.1017/erm.2025.10010Oxidative Stress and Survival of Leishmania spp.: A Relationship of Inverse Proportionality for Disease OutcomeSouravi Roy0Mayumi Mandal1Moumita Halder2Pijush K. Das3Anindita Ukil4https://orcid.org/0000-0002-1102-9437Department of Biochemistry, https://ror.org/01e7v7w47 University of Calcutta , Kolkata, IndiaDepartment of Biochemistry, https://ror.org/01e7v7w47 University of Calcutta , Kolkata, IndiaDepartment of Biochemistry, https://ror.org/01e7v7w47 University of Calcutta , Kolkata, IndiaInfectious Diseases and Immunology Division, https://ror.org/01kh0x418 CSIR – Indian Institute of Chemical Biology , Kolkata, IndiaDepartment of Biochemistry, https://ror.org/01e7v7w47 University of Calcutta , Kolkata, IndiaAbstract The development of oxidative stress depends on the deregulation of the fine balance between the proportion of reactive oxygen species (ROS) generation and the activity of antioxidants. As oxidative stress is deleterious for Leishmania sp., their host cell generates ROS as one of the foremost defence strategies. The parasites have also raised a variety of counteracting tricks in order to conquer this challenge. Upon infection, the host’s own antioxidant system is activated by the parasite to neutralise the oxidative stress-mediated protection. In addition to using the host’s antioxidant mechanisms, some genes within the parasite also make them more tolerant against oxidative stress. Therefore, the present review focuses on some major regulators intimately related to the equilibrium between oxidation and antioxidation following infection with Leishmania sp., which may be helpful in developing a comprehensive knowledge of this specific wing of infection biology associated with oxidative stress. Search Results Reactive oxygen species (ROS) play a dual role in leishmaniasis by contributing to both host defence and parasite survival mechanisms. In the host, ROS promote parasite clearance through induction of apoptosis, activation of pro-inflammatory signalling pathways (e.g., MAPK, JNK), inflammasome assembly, and M1 macrophage polarisation. Conversely, Leishmania species have evolved multiple strategies to neutralize ROS, including the upregulation of host antioxidant enzymes like HO-1, inhibition of ROS-producing pathways, and expression of parasite-derived antioxidants such as SOD, GPx, and trypanothione reductase. The parasite alsoadapts through gene regulation and metabolic changes to counter oxidative stress. Importantly, ROS have emerged as key targets for antileishmanial therapies, with various drugs and natural compounds shown to induce ROS-mediated parasite death, highlighting their potential in future therapeutic development. Conclusions In summary, the survival of Leishmania hinges on its ability to counteract host-induced oxidative stress. Targeting its antioxidant defences and enhancing host ROS production can disrupt this balance, leading to parasite death. Exploring ROS-related signalling offers a promising path for developing effective therapies against leishmaniasis. https://www.cambridge.org/core/product/identifier/S1462399425100100/type/journal_articleleishmaniasismacrophagesoxidative stressreactive oxygen species (ROS)signalling pathways
spellingShingle Souravi Roy
Mayumi Mandal
Moumita Halder
Pijush K. Das
Anindita Ukil
Oxidative Stress and Survival of Leishmania spp.: A Relationship of Inverse Proportionality for Disease Outcome
Expert Reviews in Molecular Medicine
leishmaniasis
macrophages
oxidative stress
reactive oxygen species (ROS)
signalling pathways
title Oxidative Stress and Survival of Leishmania spp.: A Relationship of Inverse Proportionality for Disease Outcome
title_full Oxidative Stress and Survival of Leishmania spp.: A Relationship of Inverse Proportionality for Disease Outcome
title_fullStr Oxidative Stress and Survival of Leishmania spp.: A Relationship of Inverse Proportionality for Disease Outcome
title_full_unstemmed Oxidative Stress and Survival of Leishmania spp.: A Relationship of Inverse Proportionality for Disease Outcome
title_short Oxidative Stress and Survival of Leishmania spp.: A Relationship of Inverse Proportionality for Disease Outcome
title_sort oxidative stress and survival of leishmania spp a relationship of inverse proportionality for disease outcome
topic leishmaniasis
macrophages
oxidative stress
reactive oxygen species (ROS)
signalling pathways
url https://www.cambridge.org/core/product/identifier/S1462399425100100/type/journal_article
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AT moumitahalder oxidativestressandsurvivalofleishmaniaspparelationshipofinverseproportionalityfordiseaseoutcome
AT pijushkdas oxidativestressandsurvivalofleishmaniaspparelationshipofinverseproportionalityfordiseaseoutcome
AT aninditaukil oxidativestressandsurvivalofleishmaniaspparelationshipofinverseproportionalityfordiseaseoutcome