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Dissertation
Small but mighty: the role of microRNAs in visceral leishmaniasis
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2025
DOI: 10.25820/etd.007953
Abstract
Visceral Leishmaniasis (VL) is a systemic disease caused by the protozoan parasite Leishmania infantum or Leishmania donovani. Thes infections cause systemic disease that dampens the patient’s immune system. VL can be complicated by Post-Kala-azar Dermal Leishmaniasis (PKDL), a macular or nodular rash that can develop after VL.
Exosomes are released from most eukaryotic cells and their content can change depending on the environment of the cell they are released from. Exosomes contain microRNAs (miRNAs); miRNAs can modify the expression of several or many mRNA transcripts by blocking translation or targeting them for degradation.
The overall hypothesis for this thesis is that miRNAs are altered during infection with Leishmania spp. that causes VL (L. donovani and L. infantum) and those miRNAs may have the ability to decrease the expression of pro-inflammatory genes, contributing to the systemic immune suppression seen in VL. This was investigated by characterizing the miRNA signatures of patients with VL, PKDL, or endemic controls in the plasma and CD4+ T-cells and assessing the expression of the miRNAs target genes. Additionally, we investigated the miRNAs in exosomes released from uninfected and infected macrophages. We show that the most abundant miRNA in VL patient plasma, miR-223-3p, is also increased in the exosomes released from infected macrophages.
Altogether, this thesis has shown that miRNAs are altered during infection with Leishmania spp. and miRNAs can decrease the expression of pro-inflammatory genes during infection. These miRNAs may lead to attenuated inflammasome activity and diminished parasite killing during infection, thereby facilitating parasite survival in the infected host.
Details
- Title: Subtitle
- Small but mighty: the role of microRNAs in visceral leishmaniasis
- Creators
- Cinthia Hudachek
- Contributors
- Mary Wilson (Advisor)Noah Butler (Committee Member)Aloysius Klingelhutz (Committee Member)Jack Stapleton (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Biomedical Science (Microbiology)
- Date degree season
- Spring 2025
- DOI
- 10.25820/etd.007953
- Publisher
- University of Iowa
- Number of pages
- xv, 129 pages
- Copyright
- Copyright 2025 Cinthia Hudachek
- Language
- English
- Date submitted
- 01/08/2025
- Description illustrations
- Illustrations, tables, graphs, charts
- Description bibliographic
- Includes bibliographical references (pages 119-129).
- Public Abstract (ETD)
Visceral Leishmaniasis (VL) is a tropical parasitic disease that can cause an infected individual to be immune-suppressed, making them more vulnerable to other infections. Post-Kala-azar Dermal Leishmaniasis (PKDL), is a rash that can develop after treatment for VL. Exosomes are small bubbles released from our cells that contain messages to send to other cells. One of these messages inside the exosomes is called miRNA, which can change the behavior of a cell.
The overall hypothesis of this thesis is that during this parasitic infection, the miRNA messages are different than people who are not infected and these differences may change the cell’s behavior. We investigate this hypothesis by characterizing which miRNAs are found within the exosomes of the blood and other specialized immune cells of patients with VL, PKDL, or uninfected people. We show that there are differences in miRNAs between these patients and that nearby cells' behavior is changed in a way that benefits the parasite in VL patients. We also profiled exosomes released from infected cells and see that they produced exosomes with similar a miRNA, miR-223-3p, seen in the blood of patients with VL and that this miRNA can alter how the cells respond to infection to make it a more hospitable environment for the parasite.
Altogether, this thesis has shown that miRNAs are altered during infection with Leishmania spp. and can lead to changing the cell’s behavior in a way that allows the parasite to potentially hide from the immune system.
- Academic Unit
- Biomedical Science Program
- Record Identifier
- 9984831231702771
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