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Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective

The leishmaniases constitute a group of parasitic diseases caused by species of the protozoan genus Leishmania. In humans it can present different clinical manifestations and are usually classified as cutaneous, mucocutaneous, and visceral (VL). Although the full range of parasite—host interactions...

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Autores principales: Poulaki, Aikaterini, Piperaki, Evangelia-Theophano, Voulgarelis, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066032/
https://www.ncbi.nlm.nih.gov/pubmed/33916346
http://dx.doi.org/10.3390/microorganisms9040759
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author Poulaki, Aikaterini
Piperaki, Evangelia-Theophano
Voulgarelis, Michael
author_facet Poulaki, Aikaterini
Piperaki, Evangelia-Theophano
Voulgarelis, Michael
author_sort Poulaki, Aikaterini
collection PubMed
description The leishmaniases constitute a group of parasitic diseases caused by species of the protozoan genus Leishmania. In humans it can present different clinical manifestations and are usually classified as cutaneous, mucocutaneous, and visceral (VL). Although the full range of parasite—host interactions remains unclear, recent advances are improving our comprehension of VL pathophysiology. In this review we explore the differences in VL immunobiology between the liver and the spleen, leading to contrasting infection outcomes in the two organs, specifically clearance of the parasite in the liver and failure of the spleen to contain the infection. Based on parasite biology and the mammalian immune response, we describe how hypoxia-inducible factor 1 (HIF1) and the PI3K/Akt pathway function as major determinants of the observed immune failure. We also summarize existing knowledge on pancytopenia in VL, as a direct effect of the parasite on bone marrow health and regenerative capacity. Finally, we speculate on the possible effect that manipulation by the parasite of the PI3K/Akt/HIF1 axis may have on the myelodysplastic (MDS) features observed in VL.
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spelling pubmed-80660322021-04-25 Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective Poulaki, Aikaterini Piperaki, Evangelia-Theophano Voulgarelis, Michael Microorganisms Review The leishmaniases constitute a group of parasitic diseases caused by species of the protozoan genus Leishmania. In humans it can present different clinical manifestations and are usually classified as cutaneous, mucocutaneous, and visceral (VL). Although the full range of parasite—host interactions remains unclear, recent advances are improving our comprehension of VL pathophysiology. In this review we explore the differences in VL immunobiology between the liver and the spleen, leading to contrasting infection outcomes in the two organs, specifically clearance of the parasite in the liver and failure of the spleen to contain the infection. Based on parasite biology and the mammalian immune response, we describe how hypoxia-inducible factor 1 (HIF1) and the PI3K/Akt pathway function as major determinants of the observed immune failure. We also summarize existing knowledge on pancytopenia in VL, as a direct effect of the parasite on bone marrow health and regenerative capacity. Finally, we speculate on the possible effect that manipulation by the parasite of the PI3K/Akt/HIF1 axis may have on the myelodysplastic (MDS) features observed in VL. MDPI 2021-04-05 /pmc/articles/PMC8066032/ /pubmed/33916346 http://dx.doi.org/10.3390/microorganisms9040759 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Poulaki, Aikaterini
Piperaki, Evangelia-Theophano
Voulgarelis, Michael
Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective
title Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective
title_full Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective
title_fullStr Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective
title_full_unstemmed Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective
title_short Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective
title_sort effects of visceralising leishmania on the spleen, liver, and bone marrow: a pathophysiological perspective
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066032/
https://www.ncbi.nlm.nih.gov/pubmed/33916346
http://dx.doi.org/10.3390/microorganisms9040759
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