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Subversion and Utilization of Host Innate Defense by Leishmania amazonensis

Infection with Leishmania amazonensis and other members of the Leishmania mexicana complex can lead to diverse clinical manifestations, some of which are relatively difficult to control, even with standard chemotherapy. Diffuse cutaneous leishmaniasis (CL) is a rare but severe form, and its clinical...

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Autor principal: Soong, Lynn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342205/
https://www.ncbi.nlm.nih.gov/pubmed/22566939
http://dx.doi.org/10.3389/fimmu.2012.00058
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author Soong, Lynn
author_facet Soong, Lynn
author_sort Soong, Lynn
collection PubMed
description Infection with Leishmania amazonensis and other members of the Leishmania mexicana complex can lead to diverse clinical manifestations, some of which are relatively difficult to control, even with standard chemotherapy. Diffuse cutaneous leishmaniasis (CL) is a rare but severe form, and its clinical hallmark is excessive parasitic growth in infected cells accompanied by profound impairments in host immune responses to the parasites. Since these parasites also cause non-healing CL in most inbred strains of mice, these animals are valuable models for dissecting the mechanisms of persistent infection and disease pathogenesis. In comparison to other Leishmania species, L. amazonensis infections are most remarkable for their ability to repress the activation and effector functions of macrophages, dendritic cells, and CD4(+) T cells, implying discrete mechanisms at work. In addition to this multilateral suppression of host innate and adaptive immunity, the activation of types I and II interferon-mediated responses and autophagic/lipid metabolic pathways actually promotes rather than restrains L. amazonensis infection. These seemingly contradictory findings reflect the remarkable adaptation of the parasites to the ancient defense machinery of the host, as well as the complex parasite–host interactions at different stages of infection, which collectively contribute to non-healing leishmaniasis in the New World. This review article highlights new evidence that reveals the strategies utilized by L. amazonensis parasites to subvert or modulate host innate defense machinery in neutrophils and macrophages, as well as the regulatory roles of host innate responses in promoting parasite survival and replication within the huge parasitophorous vacuoles. A better understanding of unique features in host responses to these parasites at early and late stages of infection is important for the rational design of control strategies for non-healing leishmaniasis.
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spelling pubmed-33422052012-05-07 Subversion and Utilization of Host Innate Defense by Leishmania amazonensis Soong, Lynn Front Immunol Immunology Infection with Leishmania amazonensis and other members of the Leishmania mexicana complex can lead to diverse clinical manifestations, some of which are relatively difficult to control, even with standard chemotherapy. Diffuse cutaneous leishmaniasis (CL) is a rare but severe form, and its clinical hallmark is excessive parasitic growth in infected cells accompanied by profound impairments in host immune responses to the parasites. Since these parasites also cause non-healing CL in most inbred strains of mice, these animals are valuable models for dissecting the mechanisms of persistent infection and disease pathogenesis. In comparison to other Leishmania species, L. amazonensis infections are most remarkable for their ability to repress the activation and effector functions of macrophages, dendritic cells, and CD4(+) T cells, implying discrete mechanisms at work. In addition to this multilateral suppression of host innate and adaptive immunity, the activation of types I and II interferon-mediated responses and autophagic/lipid metabolic pathways actually promotes rather than restrains L. amazonensis infection. These seemingly contradictory findings reflect the remarkable adaptation of the parasites to the ancient defense machinery of the host, as well as the complex parasite–host interactions at different stages of infection, which collectively contribute to non-healing leishmaniasis in the New World. This review article highlights new evidence that reveals the strategies utilized by L. amazonensis parasites to subvert or modulate host innate defense machinery in neutrophils and macrophages, as well as the regulatory roles of host innate responses in promoting parasite survival and replication within the huge parasitophorous vacuoles. A better understanding of unique features in host responses to these parasites at early and late stages of infection is important for the rational design of control strategies for non-healing leishmaniasis. Frontiers Research Foundation 2012-03-21 /pmc/articles/PMC3342205/ /pubmed/22566939 http://dx.doi.org/10.3389/fimmu.2012.00058 Text en Copyright © 2012 Soong. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Immunology
Soong, Lynn
Subversion and Utilization of Host Innate Defense by Leishmania amazonensis
title Subversion and Utilization of Host Innate Defense by Leishmania amazonensis
title_full Subversion and Utilization of Host Innate Defense by Leishmania amazonensis
title_fullStr Subversion and Utilization of Host Innate Defense by Leishmania amazonensis
title_full_unstemmed Subversion and Utilization of Host Innate Defense by Leishmania amazonensis
title_short Subversion and Utilization of Host Innate Defense by Leishmania amazonensis
title_sort subversion and utilization of host innate defense by leishmania amazonensis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342205/
https://www.ncbi.nlm.nih.gov/pubmed/22566939
http://dx.doi.org/10.3389/fimmu.2012.00058
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