New Insights on TB and COVID-19 Interactions
Study reveals how COVID-19 may influence TB control in patients.
Alba Llibre, Henna Siddiqui, Jamie Pillaye, Julie G Burel, Charlotte Jones, Harriet Hill, Sian E Faustini, Ella Windle, Hanfa Karim, Emma Sherry, Christopher A Green, Martin Dedicoat, Zania Stamataki, Adam F Cunningham, Matthew K O’Shea
― 7 min read
Table of Contents
Tuberculosis, commonly known as TB, is caused by a type of bacteria called Mycobacterium tuberculosis (often referred to as M.tb). This disease is one of the biggest killers from bacterial infections around the world. Reports show that in 2023, TB affected about 133 people for every 100,000 individuals globally, which means there were around 10.8 million new cases. Sadly, about 1.25 million people lost their lives to this disease that year alone.
TB has a special title; it is the leading cause of death from a single infectious agent. It is also known to be the biggest killer of people living with HIV. These two diseases don’t like to play alone; in 2020, the world faced a clash of pandemics with the arrival of COVID-19, caused by the SARS-CoV-2 virus. The situation got even trickier because both TB and COVID-19 can affect the lungs and share some of the same spaces in our respiratory system.
Furthermore, the COVID-19 pandemic caused a setback in the fight against TB. Many control programs for TB took a hit, resulting in fewer diagnoses and treatments. In fact, for the first time since 2005, the number of TB cases and related deaths went up. It seems like COVID-19 and TB have a complicated relationship, as both can mess with how our immune systems respond to infections.
The Study Objective
The main goal of a recent study was to better understand how the body's immune response behaves when faced with both TB and COVID-19 infections. Researchers wanted to know what happens in the early stages of TB infections and how that could potentially lead to severe cases of the disease. This part can be quite tricky to study in real-life medical settings.
In this study, researchers took whole blood samples from patients who were currently facing acute COVID-19 and then exposed these samples to mycobacteria. They measured how well the immune system managed to control the growth of the bacteria. To analyze the various immune cells at play, they used techniques called mass and flow cytometry.
Key Findings: COVID-19 Patients and Mycobacterial Growth
Surprisingly, a group of COVID-19 patients showed an improved ability to control mycobacterial growth in their blood samples. In fact, all healthy control cases managed to control the growth of mycobacteria effectively. Many COVID-19 patients performed similarly to the healthy group, but there were some who showed an even greater ability to control the infections.
Researchers were keen to explore if specific immune cell groups were responsible for this enhanced mycobacterial control. They found that COVID-19 patients tended to have lower counts of Lymphocytes, which are a type of immune cell, and higher levels of Neutrophils and Plasmablasts when compared to healthy individuals. These findings hint that the immune response in COVID-19 patients might be quite different from what we see in healthy individuals.
Immune Cell Analysis
To gather more insight, researchers closely examined the immune cell landscape using mass cytometry. They uncovered a distinct cell composition between healthy and COVID-19 patients. Among these differences, there was a notable group of cells, referred to as Population 4, that was almost absent in healthy individuals but present in COVID-19 patients. This population was identified as plasmablasts, which are important players in the immune response.
As the study progressed, researchers split the COVID-19 patients into two groups based on their ability to control mycobacterial growth: controllers and non-controllers. They found that controllers had a richer presence of a specific type of T cell, known as CD28+ CD8+ T cells, which appeared more often in patients who managed to control mycobacterial growth.
T Cell Responses and Mycobacterial Control
The research team wanted to see if the T cells from COVID-19 patients had a particular response to TB antigens. They tested if any T cells produced cytokines, which are important signaling molecules in the immune response, when exposed to TB proteins. While they did observe higher levels of cytokine production in CD8+ and CD4+ T cells from COVID-19 patients, these factors did not correlate with the ability to control mycobacterial growth.
This observation led to the conclusion that the T cells’ ability to control mycobacterial growth wasn’t solely linked to the response directed at specific TB proteins. It suggested that the immune system might be using different mechanisms to handle the infection.
The Mysterious CD28+ CD8+ T Cells
One of the interesting findings was related to the CD28+ CD8+ T cell group. Within the COVID-19 patients, those labeled as controllers had a higher number of these specific T cells, and their presence was negatively linked to mycobacterial growth. It raises the question: do these T cells have a larger role in fighting TB?
The researchers dug deeper into the characteristics of these T cells. They found that, while the controllers and non-controllers had similar activation and movement markers, the CD28+ CD8+ T cells of the controllers exhibited particular traits that could help them respond better to infections.
Implications for TB and COVID-19 Interactions
This study presents a thought-provoking look into the relationship between COVID-19 and TB. It suggests that rather than simply making individuals more vulnerable to TB, the immune response seen in some COVID-19 patients might help control mycobacterial growth. Researchers speculated that this could explain why more TB cases weren’t reported in COVID-19 patients during the pandemic.
This finding opens a new door to explore potential treatments for TB by examining how the immune response in COVID-19 patients can lead to better control of TB infections. After all, if one infection can somehow help with another, we could be onto something really interesting.
Conclusion
In summary, the study sheds light on how a portion of COVID-19 patients might have a heightened ability to control TB infections. The increased count of CD28+ CD8+ T cells in patients who showed this superior control provides a new perspective on immune interactions in the face of dual infections.
These intriguing findings could pave the way for developing new therapies for TB, particularly as we continue to navigate the impacts of the COVID-19 pandemic on public health. Researchers are now faced with the exciting task of further exploring this connection between the immune system and mycobacterial infections to improve outcomes for individuals facing both diseases.
Research Methods
The study was conducted with a clear ethical framework that involved obtaining informed consent from participants, including both COVID-19 patients and healthy controls. Blood samples were collected and analyzed to explore how the immune system responded to the presence of mycobacteria.
In the laboratory, researchers utilized a mycobacterial growth inhibition assay to measure how well whole blood could limit bacterial growth. This involved mixing blood samples with specific mycobacteria and monitoring the results.
Additionally, whole blood stimulation experiments were performed, where the samples were treated with various stimuli to activate immune responses. Researchers employed flow cytometry to evaluate T cell cytokine production and used mass cytometry to analyze the immune cell populations present in the samples.
Through these techniques, a detailed picture of the immune landscape emerged, helping researchers connect the dots between COVID-19, TB, and the immune system in ways that could have lasting impacts on treatment strategies.
Final Thoughts
The relationship between TB and COVID-19 presents a complex puzzle that researchers are just beginning to decipher. As scientists continue to untangle these interactions, we may uncover more about how our immune systems function in the face of multiple threats. Maybe one day, we’ll learn how to send viruses packing without skipping a beat!
Title: Differential control of mycobacteria among COVID-19 patients is associated with CD28+ CD8+ T cells
Abstract: Diseases caused by SARS-CoV-2 and Mycobacterium tuberculosis (M.tb) represent two public health emergencies. In severe disease, both pathogens may share a biological niche in the lower respiratory tract. There is significant potential for SARS-CoV-2 and M.tb infections to be co-present within individuals and enhance or moderate the respective outcomes of either infection. Here, we investigated how whole blood samples, as well as CD4+ and CD8+ T cells, from individuals hospitalised with acute COVID-19 disease respond to mycobacterial challenge. To do this, samples were assessed by ex vivo mycobacterial growth inhibition assays, immune cell phenotyping by mass cytometry, and whole blood cytokine responses to mycobacterial antigens assessed by flow cytometry. These studies identified a subgroup of COVID-19 patients whose blood had an enhanced capacity to inhibit mycobacterial growth. The ability to control mycobacterial growth was associated with the presence of a non M.tb-specific CD28+ CD8+ T cell population, with a particular activation status and migratory phenotype. This work improves our understanding of factors involved in mycobacterial control, and may contribute to the design of novel therapies for TB.
Authors: Alba Llibre, Henna Siddiqui, Jamie Pillaye, Julie G Burel, Charlotte Jones, Harriet Hill, Sian E Faustini, Ella Windle, Hanfa Karim, Emma Sherry, Christopher A Green, Martin Dedicoat, Zania Stamataki, Adam F Cunningham, Matthew K O’Shea
Last Update: Dec 10, 2024
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.12.09.626962
Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.09.626962.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.
Thank you to biorxiv for use of its open access interoperability.