Lungs and Long-Term Effects of IAV Infection
How IAV infection alters lung cells and immune responses long-term.
Megan KL MacLeod, J. C. Worrell, K. E. Hargrave, G. E. Finney, C. Hansell, J. J. Cole, J. Singh Niijar, F. R. Morton, M. Pingen, T. Purnell, K. Mitchelson, E. Brennan, J. Allan, G. Ilia, V. Herder, C. Kennedy Dietrich, Y. Doncheva, N. Jamieson, M. Palmarini
― 7 min read
Table of Contents
- Long-Term Changes in Lung Cells After IAV Infection
- The Epithelial and Structural Response to IAV
- Specific Gene Changes Observed
- The Role of SpiB in the Lung's Immune Memory
- How IAV Infection Affects T Cell Interactions
- Findings on Immune Functionality in Epithelial Cells
- Structural Changes in Lung Cells After Infection
- Interaction Between Immune Cells and Lung Structure
- Implications for Future Research
- Conclusion
- Original Source
- Reference Links
Lungs are constantly interacting with various microbes, including viruses. One major virus that affects the lungs is the influenza A virus (IAV), which can cause significant disease worldwide. The World Health Organization estimates that each year, IAV leads to millions of cases of severe illness and hundreds of thousands of deaths. To fight off infections, the lungs rely on many different types of cells. These include structural cells, which make up lung tissue, and various Immune Cells.
When IAV infects the lungs, it primarily targets Epithelial Cells, the cells lining the airways. These cells play a crucial role in the immune response. They release signals that help manage the infection and summon immune cells to the site of infection. Blood vessel cells, known as endothelial cells, also help by attracting circulating immune cells to the lungs when needed.
IAV infection typically clears within a week or so, but the effects of the virus can linger for much longer. For example, while some lung cells work to heal damaged tissue, the damage itself can last for months. Additionally, certain immune cells can stay in the lungs long after the virus is gone, helping the body respond to future infections. This phenomenon is part of what we call "immunity."
Long-Term Changes in Lung Cells After IAV Infection
Recent research has shown that even structural lung cells can change in response to an IAV infection. Some cells, like certain epithelial cells, have shown lasting effects from the infection, which might help them respond more effectively if the virus attacks again. These findings indicate that there is a potential memory effect in lung cells, similar to that seen in immune cells.
To better understand how IAV affects lung cells over time, scientists conducted a study where they looked at different lung cell types after an infection and even after re-infection. They isolated specific types of structural cells and analyzed their genetic material to see how Gene Expression changes after infection.
The study found that many genes important for fighting infections were still active, long after the initial viral infection had cleared. Specifically, researchers noticed that epithelial cells, along with fibroblasts (another type of lung cell), still showed signs of the infection 40 days later. This suggests that these cells can "remember" the infection and might be better able to respond to future threats.
The Epithelial and Structural Response to IAV
Epithelial cells are the primary targets for IAV. When infected, they play a critical role in the immune response. Along with nearby fibroblasts, they release signals that help regulate inflammation and recruit immune cells. The study highlighted that after an infection, there is a noticeable increase in the expression of certain genes linked to the body’s defense against viruses.
In the first ten days after an IAV infection, significant changes in gene expression were observed. Many genes related to fighting viruses were activated in the lung cells. For instance, epithelial cells showed a robust response in terms of gene expression changes, indicating that they are ready to fight off the virus.
As time passed, researchers continued to observe changes in gene expression even at the 40-day mark. Although the number of active genes decreased compared to early post-infection, many genes remained elevated, especially in epithelial and fibroblast cells. This points to a potential long-term adjustment of the lung's defense mechanisms following infection.
Specific Gene Changes Observed
In the analysis, several genes that had increased expression after infection were linked to processes involved in recognizing and battling viruses. For instance, many genes associated with inflammation and the immune response were upregulated. The study also pointed out a significant overlap in the genes that remained elevated for both fibroblasts and epithelial cells after the IAV infection.
Interestingly, even the blood vessel cells in the lungs showed a prolonged expression of immune-related genes, suggesting a coordinated response among all types of lung cells.
The Role of SpiB in the Lung's Immune Memory
Researchers identified a particular transcription factor known as SpiB that seemed to play a vital role in these long-term changes in gene expression. SpiB is involved in regulating genes that help process and present antigens, which are crucial for the immune response.
They found that a notable portion of the genes that remained active after IAV infection were targets of SpiB. This indicates that SpiB may contribute to the memory of the immune system within lung cells, helping them respond more effectively during future infections.
How IAV Infection Affects T Cell Interactions
T cells are a critical part of the immune response and help eliminate infected cells. In the case of IAV re-infection, T cells can recognize previously encountered viral components, aiding in faster control of the virus. In the study, scientists observed that while T cells are important for responding to infections, the epithelial cells themselves also show an enhanced ability to control IAV, even without initial T cell help.
After a re-infection, lung epithelial cells from previously infected mice could control the virus more rapidly. This was because these cells had already "learned" from the prior infection. They adapted their ability to communicate with T cells more efficiently, enhancing the immune response.
Findings on Immune Functionality in Epithelial Cells
The research highlighted that immune responses can be influenced by prior infections. In scenarios where mice were re-infected with a different strain of IAV, the epithelial cells exhibited less virus than those from primary infected animals. This suggests that the lungs' structural cells have a level of memory, allowing for a quicker and more effective response during subsequent infections.
Moreover, while T cells significantly contribute to the protective response, the study indicated that these structural cells could manage to control the virus on their own. This dual ability shows that both the immune system and lung cells work together to provide a comprehensive defense against respiratory viruses.
Structural Changes in Lung Cells After Infection
The study also investigated how structural changes in lung cells occurred after IAV infection. Researchers used various techniques to analyze changes at the cellular level. They noticed that different subtypes of epithelial cells responded uniquely to the IAV infection.
For example, certain ciliated cells and progenitor cells were more likely to express MHC class II molecules, which are crucial for presenting antigens to T cells. This suggests that these epithelial cell subtypes are equipped to better communicate with the immune system in response to infections.
Interaction Between Immune Cells and Lung Structure
In analyzing the relationship between immune cells and lung structural cells, researchers saw that IAV infection led to an enhanced interaction between these cells. Specifically, они found that structural cells could not only present antigens but also alter their behaviors and functions based on the presence of immune cells.
The findings indicate that structural lung cells can quickly adapt to an infection, display changes in gene expression, and maintain communication with various immune cell types. This adaptability showcases their vital role in the lung's defense mechanisms against infections.
Implications for Future Research
The study's findings open the door for further research into how lung cells exhibit memory and enhance their immune responses. Understanding the interplay between structural cells and immune cells can lead to new strategies for treating respiratory infections and developing effective vaccines.
Since structural lung cells show lasting changes after IAV infection, it suggests a need to consider these cells when designing future immunotherapies or vaccines. By harnessing the knowledge of how these cells respond and adapt to infections, we can potentially improve vaccination strategies and enhance overall respiratory health.
Conclusion
In summary, the lungs exhibit dynamic and complex responses to IAV infections. Structural cells, including epithelial cells and fibroblasts, show lasting changes that empower them to better control future infections. The findings indicate that not only immune cells but also structural lung cells play critical roles in forming a robust defense against respiratory viruses.
As research continues, a deeper understanding of these interactions will be crucial for developing innovative prevention and treatment methods for respiratory diseases. The lung's ability to adapt and remember past infections underscores the importance of both cellular and immunological responses in maintaining respiratory health.
Title: Lung structural cell dynamics are altered by influenza virus infection experience leading to rapid immune protection following viral re-challenge
Abstract: Lung structural cells, including epithelial cells and fibroblasts, form barriers against pathogens and trigger immune responses following infections such as influenza A virus. This response leads to the recruitment of innate and adaptive immune cells required for viral clearance. Some of these recruited cells remain within the lung following infection and contribute to enhanced viral control following subsequent infections. There is growing evidence that structural cells can also display long-term changes following infection or insults. Here we investigate long-term changes to mouse lung epithelial cells, fibroblasts, and endothelial cells following influenza virus infection and find that all three cell types maintain an imprint of the infection, particularly in genes associated with communication with T cells. Lung epithelial cells from IAV-infected mice display functional changes by more rapidly controlling influenza virus than cells from naive animals. This rapid anti-viral response and increased expression of molecules required to communicate with T cells demonstrates sustained and enhanced functions following infection. These data suggest lung structural cells could be effective targets for vaccines to boost durable protective immunity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/604410v5_ufig1.gif" ALT="Figure 1"> View larger version (55K): [email protected]@6a39e6org.highwire.dtl.DTLVardef@1ff5863org.highwire.dtl.DTLVardef@103df12_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LILung epithelial cells, fibroblasts, and blood endothelial cells maintain an inflammatory imprint of influenza A virus (IAV) infection for at least 40 days post-infection. C_LIO_LIIn vivo re-infection leads to a more spatially restricted anti-viral response compared to primary IAV-infected animals. C_LIO_LIT cells are not required for enhanced viral control early after re-infection in vivo C_LIO_LIEx vivo lung epithelial cells from IAV-infected mice more rapidly control IAV than cells from naive animals in the absence of immune cells. C_LI
Authors: Megan KL MacLeod, J. C. Worrell, K. E. Hargrave, G. E. Finney, C. Hansell, J. J. Cole, J. Singh Niijar, F. R. Morton, M. Pingen, T. Purnell, K. Mitchelson, E. Brennan, J. Allan, G. Ilia, V. Herder, C. Kennedy Dietrich, Y. Doncheva, N. Jamieson, M. Palmarini
Last Update: 2024-10-26 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.07.20.604410
Source PDF: https://www.biorxiv.org/content/10.1101/2024.07.20.604410.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.