E. histolytica: The Intriguing Parasite's Strategy
A look at how E. histolytica communicates with the immune system.
Barbara Honecker, Valentin A. Bärreiter, Katharina Höhn, Balázs Horváth, Karel Harant, Nahla Galal Metwally, Claudia Marggraff, Juliett Anders, Stephanie Leyk, Maria del Pilar Martínez-Tauler, Annika Bea, Charlotte Hansen, Helena Fehling, Melanie Lütkemeyer, Stephan Lorenzen, Sören Franzenburg, Hanna Lotter, Iris Bruchhaus
― 6 min read
Table of Contents
- What Are Extracellular Vesicles?
- The Disease: Amebiasis
- Who Gets Hit Harder by This Parasite?
- Exploring E. Histolytica EVs
- Research Objectives
- Particle Release and Size
- Visualizing EVs
- Proteins in EVs
- Micro RNAs in EVs
- Monocyte Response to EVs
- The Gender Factor
- Myeloperoxidase Release
- Conclusion
- Original Source
- Reference Links
E. Histolytica is a tiny parasite responsible for a disease known as amebiasis, which mainly affects folks in tropical regions. If you happen to eat or drink anything contaminated with this parasite, you might end up with an upset stomach or, in severe cases, more serious issues like dysentery or liver abscesses. Now, that's a mouthful! The good news is that most people who get infected don’t show symptoms, but for those who do, it could be a real problem.
Extracellular Vesicles?
What AreSo, how does this tiny troublemaker communicate with the immune system? It does so with the help of something called extracellular vesicles (EVs). These tiny bubbles, made from the wall of cells, can carry useful information like proteins and RNA from one cell to another. Think of EVs as tiny envelopes delivering messages between the parasite and the body’s immune defenders.
E. histolytica releases these EVs, which plays a role in whether the parasite sticks around or gets kicked out. Interestingly, researchers have been studying these EVs to see if they could even help create vaccines.
The Disease: Amebiasis
Now, let’s dive a little deeper into amebiasis. E. histolytica is the bad guy here, and it’s the cause of this disease. According to some numbers out there, it causes around 26,000 deaths every year worldwide. Most infections, however, are asymptomatic, meaning you wouldn't even know you had it. In rare cases, though, it becomes invasive, leading to severe conditions like dysentery or liver abscesses. That’s when things get serious!
Who Gets Hit Harder by This Parasite?
You may wonder why some people get really sick while others don't, even after being exposed. Studies show that adult men are more likely to develop complications than women, even when infection rates are similar. This seems to have a lot to do with certain immune cells called Monocytes.
In a mouse model study, when researchers depleted these immune cells, the size of the abscesses shrank. It appears that male mice had more of these inflammatory monocytes showing up in the liver than female mice, suggesting a different immune response connected to the rather male hormone testosterone.
Exploring E. Histolytica EVs
Not many studies have looked at E. histolytica EVs yet. However, some early research suggests that these EVs can change how immune cells, like macrophages and neutrophils, react. For instance, when these EVs interact with macrophages, they seem to suppress a certain immune response, leading to a lower activation of the immune cells.
This is interesting because a different pathogen that targets reptiles, Entamoeba invadens, shows that EVs might help amebae communicate about their life cycles. So, there seems to be a lot happening in the background when these parasites use EVs.
Research Objectives
The main goal of the recent studies has been to understand how E. histolytica EVs interact with monocytes, which are crucial players in the immune response during liver infections. Researchers compared two different clones of the parasite known for their varying abilities to cause disease: the less harmful EhA1 and the more dangerous EhB2.
By analyzing these EVs and their cargo, researchers aimed to uncover potential differences between the two clones that could explain why some infections are worse than others.
Particle Release and Size
To get a better idea of the EVs produced by these clones, scientists isolated the particles, characterizing them by size and shape. They found that the majority of released vesicles ranged between 80 and 400 nanometers in size. Both clones released similar-sized EVs, which suggests they may share certain characteristics in terms of how they produce and release these particles.
Visualizing EVs
To confirm their findings, researchers also used fancy imaging techniques like transmission electron microscopy. They could see the EVs and confirm they had markers on their surfaces indicating they came from the E. histolytica parasite.
Proteins in EVs
Going even further, researchers wanted to understand what types of proteins are found in the EVs from EhA1 and EhB2. They discovered nearly 900 different proteins in total, many of which might play a role in the parasite's ability to infect or cause problems in the host.
Comparing these proteins revealed that while many were common to both clones, there were some unique ones too. For instance, some proteins known for their roles in signaling and transport were more abundant in specific clones, hinting at possible differences in how each clone interacts with the immune system.
Micro RNAs in EVs
But wait, there’s more! Besides proteins, the EVs also contained micro RNAs (miRNAs). These small pieces of RNA can influence how genes are expressed in other cells. Researchers discovered that the parasite pushes out a whole new set of miRNAs that were previously unknown, meaning that E. histolytica is probably influencing its environment in ways we didn't realize.
Monocyte Response to EVs
Researchers wanted to see how these EVs affect monocytes, the immune cells that are the first responders to infection. After exposing these cells to EVs, they found that many genes associated with inflammation and immune responses were switched on. It was like flipping a light switch to turn on the immune system!
Interestingly, both clones of EVs stimulated fairly similar responses in monocytes, leading to increased production of various inflammatory cytokines. This was despite the fact that one clone is known for being much more pathogenic than the other. So, it seems that both clones know how to trigger a reaction from those immune cells!
The Gender Factor
When it comes to how male and female monocytes respond to these EVs, the studies showed that male monocytes tend to release more cytokines, reinforcing the idea that male mice might be more susceptible to the aggressive behavior of E. histolytica.
Myeloperoxidase Release
One of the key findings was related to an enzyme called myeloperoxidase (MPO), which plays a crucial role in how the immune system fights off infections. Researchers found that only the less pathogenic clone, EhA1, managed to get monocytes and neutrophils to release more MPO. This raises questions about what’s happening with the more pathogenic clone and why it doesn’t trigger the same response.
Conclusion
In wrapping up these findings, we observe that E. histolytica is a tricky little parasite that not only affects its host directly but also sends out messengers in the form of EVs. These tiny envelopes carry proteins and RNA, communicating with the immune system in ways that can lead to inflammation and, ultimately, disease.
Unraveling how these processes work could help scientists figure out better treatment strategies or even vaccines for amebiasis. In the end, understanding this parasite is a bit like piecing together a jigsaw puzzle – you can see the big picture only after examining every tiny piece, no matter how microscopic.
Original Source
Title: Entamoeba histolytica extracellular vesicles drive pro-inflammatory monocyte signaling
Abstract: The parasitic protozoan Entamoeba histolytica secretes extracellular vesicles (EVs), but so far little is known about their function in the interaction with the host immune system. Infection with E. histolytica trophozoites can lead to formation of amebic liver abscesses (ALAs), in which pro-inflammatory immune responses of Ly6Chi monocytes contribute to liver damage. Men exhibit a more severe pathology as the result of higher monocyte recruitment and a stronger immune response. To investigate the role of EVs and pathogenicity in the host immune response, we studied the effect of EVs secreted by low pathogenic EhA1 and highly pathogenic EhB2 amebae on monocytes. Size and quantity of isolated EVs from both clones were similar. However, they differed in their proteome and miRNA cargo, providing insight into factors potentially involved in amebic pathogenicity. In addition, EVs were enriched in proteins with signaling peptides compared with the total protein content of trophozoites. Exposure to EVs from both clones induced monocyte activation and a pro-inflammatory immune response as evidenced by increased surface presentation of the activation marker CD38 and upregulated gene expression of key signaling pathways (including NF-{kappa}B, IL-17 and TNF signaling). The release of pro-inflammatory cytokines was increased in EV-stimulated monocytes and more so in male-than in female-derived cells. While EhA1 EV stimulation caused elevated myeloperoxidase (MPO) release by both monocytes and neutrophils, EhB2 EV stimulation did not, indicating the protective role of MPO during amebiasis. Collectively, our results suggest that parasite-released EVs contribute to the male-biased immunopathology mediated by pro-inflammatory monocytes during ALA formation. Author summaryParasites communicate with their host via small membranous extracellular vesicles (EVs) that can shuttle cargo and thus information between cells. The protozoan parasite Entamoeba histolytica releases EVs but not much is known about their role in the interaction with the host immune system. Infection with E. histolytica can lead to amebic liver abscess (ALA) formation. Innate immune cells, particularly monocytes, contribute to liver damage by releasing microbicidal factors. Men have a more severe ALA pathology as the result of a stronger monocyte immune response. In this study, we analyzed the effect of EVs from differently virulent E. histolytica clones on monocytes to better understand their interaction. EVs of both clones were similar in size and quantity but differed in their cargo, which provides information on factors potentially involved in pathogenicity. Monocytes responded to EVs of both clones in a pro-inflammatory manner that reflected the immune processes occurring during ALA in vivo, including the bias towards the male sex. Only EVs of amebae with low pathogenicity, and not those released by the highly pathogenic clone, elicited secretion of the granular enzyme myeloperoxidase, which plays a protective role during ALA. Overall, our data suggest that EVs may contribute to liver injury.
Authors: Barbara Honecker, Valentin A. Bärreiter, Katharina Höhn, Balázs Horváth, Karel Harant, Nahla Galal Metwally, Claudia Marggraff, Juliett Anders, Stephanie Leyk, Maria del Pilar Martínez-Tauler, Annika Bea, Charlotte Hansen, Helena Fehling, Melanie Lütkemeyer, Stephan Lorenzen, Sören Franzenburg, Hanna Lotter, Iris Bruchhaus
Last Update: 2024-12-24 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.12.24.630232
Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.24.630232.full.pdf
Licence: https://creativecommons.org/licenses/by/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
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