Share on PinterestNew research explains the mechanism behind why we’re more prone to colds and flu in winter. Image Credit: Erhan Demirtas/NurPhoto via Getty Images.Fall and winter are associated with a higher incidence of upper respiratory infections, such as the common cold and flu, due to increased transmission of respiratory viruses.Although cooler temperatures and low humidity are associated with increased susceptibility to respiratory viruses, the biological mechanisms underlying this relationship are not understood.A recent study showed that cold temperatures lead to a decreased immune response elicited by cells in the nasal cavity to viruses, which explains why people are more susceptible to upper respiratory tract infections in colder temperatures. .
Scientists have been trying to explain the biological mechanisms behind the increased incidence of common colds and flu during winter.
And now, a study published in the Journal of Allergy and Clinical Immunology describes a mechanism in the nose that could explain the increased susceptibility to upper respiratory tract infections during the winter.
Previous studies by the current author have found that one component of the immune response against respiratory viruses involves the release of swarms of membrane-bound particles called extracellular vesicles (EVs) by cells lining the nasal cavity.
EVs are membrane-bound particles that can carry a payload of DNA, RNA, and protein and are released by most cell types and help produce an antiviral response. miRNAs, a type of RNA, do not code for proteins but can regulate the expression of target genes.
In the nose, EVs can prevent viruses from binding to uninfected cells or transferring their payload to uninfected cells and modulate their immune response.
In the current study, winter-like temperatures resulted in lower temperatures, 37 to 32 degrees Celsius, in the nasal cavity, which weakened this immune response.
Specifically, this 5 degree drop in temperature within the nasal cavity attenuated EV release and the antiviral response mediated by these EVs, explaining the increased susceptibility to common colds in winter.
Lead study author Dr. Benjamin Bleier, an associate professor of otolaryngology at Harvard Medical School, told Medical News Today: “We found that this drop significantly reduced this innate immune response in the nose, decreasing not only the amount “It’s not the quality of extracellular vesicles swarming with the virus. This reduced response may make the virus better able to attach to and then infect nasal cells, where it can then divide and cause infection.”
“We believe these findings offer one of the first true mechanistic biological explanations for why people are more likely to contract colds and other viruses that cause upper respiratory tract infections in colder climates.”
— Dr. Benjamin Bleier
Previous studies have shown that upper respiratory tract infections, including the common cold and flu, are more common in the colder seasons.
This has been attributed to increases in upper respiratory virus transmission due to changes in temperature and humidity and human behavior such as spending more time indoors.
However, more recent studies suggest that cold temperatures could attenuate the immune response elicited by the upper respiratory tract to these viruses, resulting in increased susceptibility to infections.
Due to its proximity to the external environment, the nasal cavity is more sensitive to changes in ambient temperature than the rest of the body, including the lungs.
An earlier study reported that rhinoviruses, the most common cause of upper respiratory tract infections, can replicate more efficiently at lower temperatures in the nasal cavity than at higher temperatures.
The study also reported that infected cells lining the nasal cavity produced a weaker immune response at 33 degrees Celsius than at 37 degrees Celsius.
However, the mechanisms linking changes in environmental factors with increased susceptibility to the common cold are not well understood.
In the present study, the researchers further examined how temperature changes might modulate the immune response elicited by the upper respiratory tract.
The nasal cavity is lined with the nasal mucosa, or mucous membrane, which secretes mucus. The nasal mucosa is the first site of contact for inhaled respiratory microbes and plays a critical role in protection against infection.
The nasal mucous membrane can physically prevent the entry of microbes and secrete molecules with antimicrobial properties into the mucus.
Nasal epithelial cells, which are part of the mucosal membrane, also express toll-like receptors (TLRs) on their surface, which can activate the innate immune response.
The innate immune response is the first line of defense against pathogens and is non-specific. TLRs can recognize structural patterns in microbial proteins or toxins and trigger an immune response by stimulating the production of immune proteins.
In previous studies, the authors of the current research demonstrated that activation of TLR4, a type of toll-like receptor activated by bacterial toxins, can stimulate the release of a swarm of EVs.
In their research, they found that activation of toll-like receptors resulted in the release of electric vehicles that triggered a defensive response against pathogenic bacteria.
These EVs can carry proteins that can bind to and neutralize microbes, and can donate their cargo to neighboring or more distant cells to enhance the immune response.
The study authors first characterized the role of EVs produced upon TLR activation in mediating an immune response against respiratory viruses.
They carried out these experiments using laboratory-grown human nasal epithelial cells.
To examine whether EVs are released in response to respiratory viruses, the researchers stimulated TLR3, a toll-like receptor that is specifically activated by viral RNA.
They stimulated TLR3 using polyinosinic:polycytidylic acid (poly I:C), which is a substance that resembles viral RNA.
TLR3 stimulation increased EV secretion by nasal epithelial cells. The researchers then isolated and purified these TLR3-stimulated EVs and tested their antiviral activity against three common respiratory viruses: rhinoviruses RV-1B and RV-16, and the coronavirus CoV-OC43.
The researchers found that exposure to TLR3-stimulated EV isolates suppressed infection of cultured human nasal epithelial cells by these respiratory viruses.
By tagging the EVs with a fluorescent label, the researchers found that isolated TLR3-stimulated EVs were internalized by other nasal epithelial cells that were not exposed to poly I:C.
In other words, the charge carried by these electric vehicles could reach uninfected cells.
The researchers found that TLR3-stimulated EVs showed higher levels of six microRNAs than EVs from unstimulated cells.
In particular, one of the six miRNAs, miR-17, has been shown to suppress viral replication. Furthermore, downregulation of miR-17 levels in EVs reduced the antiviral activity of TLR3-stimulated EVs against human nasal epithelial cells infected with any of the three common cold viruses.
This shows that the miRNA cargo carried by the TLR3-stimulated EVs was transferred to other cells, where it helped generate an antiviral response.
Previous studies have also shown that EVs can express cell surface receptors that viruses use to enter cells. The expressed receptors can act as decoys and reduce the number of virus particles that can then infect cells.
In the present study, surface receptor proteins involved in RV-1B and RV-16 rhinovirus entry were more abundant in TLR3-stimulated EVs than in unstimulated vesicles. Furthermore, incubation of TLR3-stimulated EVs with RV-1B and RV-16 reduced the ability of these viruses to infect human nasal epithelial cells.
The researchers also found that these respiratory viruses directly interacted with cell surface receptors expressed by TLR3-stimulated EVs.
These findings suggest that the expression of these cell surface receptors by EVs potentially prevented the virus from subsequently infecting other cells.
The researchers then examined the impact of cold environmental temperatures on this EV-mediated antiviral immune response. They first used endoscopy to assess temperature changes within the nasal cavity of healthy individuals in response to the low temperatures typically seen during winter.
A drop in ambient temperature from 23.3 degrees Celsius to 4.4 degrees Celsius was associated with a drop in temperature inside the nasal cavity of about 5 degrees Celsius.
The researchers simulated this 5 degree Celsius drop in intranasal temperatures in the laboratory by growing human nasal mucosal cells at 32 degrees Celsius instead of 37 degrees Celsius.
Lowering the temperature reduced the release of EVs in response to TLR3 stimulation. Human nasal mucosal tissue explants, which are pieces of nasal tissue rather than cells grown in the laboratory, also showed a similar decrease in EV secretion at 32 degrees Celsius compared to 37 degrees Celsius.
Incubation of nasal epithelial cells at 32 degrees Celsius also reduced the abundance of miR-17 in EVs released after TLR-3 stimulation. In addition, temperature reduction reduced the expression of surface receptor proteins on TLR3-stimulated EVs that could serve as decoys.
Thus, exposure to cooler environmental temperatures may attenuate not only TLR3-stimulated EV release by nasal epithelial cells, but also reduce the abundance of packaged antiviral miRNA and cell surface protein expression by nasal epithelial cells. ev.
These results could facilitate a better understanding of respiratory infections, as well as other conditions.
Dr. Santosh Kumar, a professor at the University of Tennessee Health Sciences Center, told MNT that:
“The study shows an important role of nasal epithelial extracellular vesicles (EVs) in sensitivity to viral or other infections and perhaps a self-defense mechanism via TLR. Furthermore, the biology of EVs via TLR can change depending on the presence of infectious agents or seasonal allergens. This provides an adaptive biological role for nasal epithelial EVs. The findings may also be generalized to other EVs generated by other organs/tissues following exposure to other agents.”
Source: news.google.com