1. Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective
- Author
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Evangelia-Theophano Piperaki, Michael Voulgarelis, and Aikaterini Poulaki
- Subjects
bone marrow dysplasia ,0301 basic medicine ,Microbiology (medical) ,Spleen ,Review ,Biology ,liver ,Microbiology ,pancytopenia ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Virology ,medicine ,visceral leishmaniasis ,leishmaniasis ,lcsh:QH301-705.5 ,immunobiology ,PI3K/AKT/mTOR pathway ,Leishmaniasis ,medicine.disease ,Leishmania ,biology.organism_classification ,microenvironment ,Pancytopenia ,030104 developmental biology ,Visceral leishmaniasis ,medicine.anatomical_structure ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Immunology ,spleen ,Bone marrow - Abstract
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.
- Published
- 2021