Category Archives: Health

Have you, as I have, noticed that many of your friends and acquaintances are sick this winter? Or maybe you yourself got the cold or flu?

We are told that it’s an old wife’s tale that cold weather makes us sick.

Well, it turns out that the old wife’s tale is true!

A new study, “Cold exposure impairs extracellular vesicle swarm–mediated nasal antiviral immunity,” coauthored by six scientists, published in The Journal of Allergy and Clinical Immunology, Dec. 6, 2022, found the underlying biological mechanisms for why there is seasonal variation in respiratory viral infections.

Below are excerpts from the article:

Upper respiratory tract infections (URIs) pose a significant public health burden in terms of decreased productivity, absenteeism at work or school, and health care system overload. URIs may be associated with multiple clinical sequelae, such as otitis media, sinusitis, bronchiolitis, pneumonia, and exacerbation of asthma or chronic obstructive pulmonary disease.…

Seasonal variation in increased URI prevalence, morbidity, and mortality during the winter period has been well recognized. These adverse outcomes may be further exacerbated by socioeconomic and behavioral factors as well as age, sex, and comorbidities…. Accumulating evidence suggests that temperature and humidity may independently or jointly contribute to the risk of respiratory viral infections due to changes in host susceptibility. Similarly, recent fundamental research exploring the underlying molecular mechanisms demonstrates that cold temperature may impair host innate immune response to viral infections.

The nasal cavity is one of the initial contact points between the external environment and the human body; it is highly sensitive to changes in ambient temperature. The nasal mucosal barrier therefore represents the front line of defense against exposure to inhaled respiratory pathogens through multiple host immune mechanisms. The physical barrier function of the nasal mucosa can prevent pathogens from entering the body through the production of mucus glycoproteins, mucociliary clearance, and epithelial tight junctions. The nasal epithelial cells also play important roles in the initiation, maintenance, and regulation of innate immunity. These defense mechanisms are constitutive and can be activated by both membrane-bound and cytoplasmic pattern recognition receptors that recognize pathogen-associated molecular patterns commonly found in viruses. One of the best characterized classes of pattern recognition receptors is the Toll-like receptor (TLR)family, which are transmembrane receptors expressed on multiple cell types, including nasal epithelial cells. TLRs recognize components of invading microbes and trigger the first line of innate immune and inflammatory responses to combat infectious agents. Within the TLR family, TLR3 is considered a major mediator of cellular defense to viral infection, as it responds to double-stranded RNA (dsRNA), a common by-product of virus replication. While these strategies occur at the level of the epithelial cell, recent evidence has shown that active host mucosal defense to bacteria extends into the mucus itself through the epithelial release of antimicrobial extracellular vesicle (EV) swarms. EVs are lipid-bound vesicles secreted by cells into the extracellular space and have been reported in virtually all human biological fluids, including blood, lymph, and nasal mucus…. Accumulating evidence has shown that in addition to their previously described antibacterial role, EVs may also regulate innate immune responses to viral infections. This occurs through the functional delivery of antiviral agents, such as microRNAs (miRNAs), into neighboring or distant recipient cells…. Previous studies have reported that several miRNAs have direct antiviral effects or regulate the inflammatory pathways, thereby enhancing antiviral immunity against infections. In addition to transport of antiviral agents between cells, EVs can also exert direct virion neutralization by binding to virus ligands via surface receptors and block their entry to host cells.

The scientists ran a number of experiments and found that when the temperature is reduced by as little as 5 degrees Centigrade, “Cold exposure impairs TLR3-dependent EV secretion and miR-17 abundance, which abrogates antiviral activity.” In other words, exposure to cold temperature impairs the body’s secretion of the extracellular vesicles (EV) that regulate our bodies’ innate immune responses to viral infections. 

The study concludes:

[T]he potent antiviral functions mediated by TLR3-dependent EVs are impaired by cold air conditions via a 41.9% decrease in total EV release as well as reduced miRNA packaging (23.8%) and antiviral surface receptor binding activity (24.4% and 77.2%) of individual EV….

Many respiratory viruses initiate infection in the nasal cavity, which is the first region of contact of inhaled respiratory pathogens and is highly sensitive to changes in ambient air temperature. The diminished innate immune responses to viral infections at cool temperatures could thereby create a more permissive environment for virus replication compared to warm temperatures…. [I]nhaling cool air in the winter season might impair the antiviral immune defense functions mediated by TLR3-stimulated EVs and decrease resistance to infections by reducing the host cell temperature within the anterior nasal mucosa. Our observations revealed that exposure to cold resulted in increased host susceptibility to respiratory viruses, providing a potential immunologic mechanism for seasonal variation in URIs.

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