Why are you easy to catch a cold?

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Apr 11, 2019
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A recent development in a new study published in Cell Reports explains why some people are more likely to catch a cold than others: Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus. The article was post by Yale University. The results confirmed the differences in the response of different cells to rhinovirus.

Rhinovirus is the main cause of the common cold and can cause asthma and other respiratory related diseases. Human rhinovirus (HRV) belongs to the small RNA virus and has been identified by more than 120 types. It is the virus with the most serum antigen type in human viruses. After the human body is infected with rhinovirus, it may acquire immunogenicity, but the maintenance time is short, and there is no cross protection between different rhinovirus types, so some people may have multiple colds. After being infected by rhinovirus, some people may have mild cold symptoms such as runny nose, stuffy nose and sore throat. Some people may suffer from severe cold symptoms such as fatigue and bed rest.

In previous studies, it was demonstrated that there is a respiratory virus in the human nasal cavity, but it is usually cleared without causing symptoms.In a monitoring data, 44% of people were asymptomatic after being infected with the virus. That is to say, the respiratory defense response can effectively remove the virus infection locally without excessive inflammation and a large amount of viscous traits. When human respiratory epithelial cells are infected with rhinovirus, they produce a variety of cytokines and chemokines, which promote the recruitment and activation of inflammatory and immune effector cells.

To better understand the molecular mechanisms of antiviral defense responses in the respiratory tract, this study focused on the interrelationship between epithelial cells and rhinoviruses.

The innate defense of airway epithelial cells can effectively block viral replication and clear infections early in rhinovirus infection. As a target cell for rhinovirus replication, after infection, the interferon-stimulated gene (ISG) is activated to induce the expression of type I and type III interferon (IFN), causing programmed cell death, thereby inhibiting the proliferation of rhinovirus. It has also been reported that epithelial interferon response caused by RNA virus infection can attenuate cold symptoms such as asthma and smokers, further confirming that epithelial cell innate defense is essential for controlling rhinovirus infection.

In this study, epithelial cells were harvested from the nasal and bronchus of healthy donors and cultured in the same environment to analyze the antiviral response of these epithelial cells. When low-passage cells were infected with rhinovirus 1B (RV1B), it was found that nasal epithelial cells were more potent in secreting type III interferon IFNλ1 than bronchial epithelial cells, and IFNλ1 was cultured at 33 °C. The secretion will be reduced. Interestingly, the level of IFNλ1 secretion by nasal cells at 33 °C was comparable to that of bronchial cells at 37 °C. When the cells were transfected with SLR14, the two cells were cultured at the same temperature, and the results showed that the expression levels of IFNλ1, IFNβ, and OAS1 were higher in the nasal cells than in the bronchial cells.

RIG-I is a receptor in the cell that recognizes abnormal mRNA of the virus and can cause cell damage by viruses and other inhalation stimuli such as cigarette smoke or tree pollen. Using RIG-I virus surveillance pathways triggered by nasal and bronchial cells, the researchers found that both cells produced antiviral responses and defense responses against oxidative stress, and that antiviral responses were stronger in nasal cells. In bronchial cells, the defense against oxidative stress is more pronounced.

In order to explain the difference in response to RIG-I stimulation of epithelial cells in the nasal or bronchial region, the transcriptomes of normal and SLR14-stimulated cells were compared by RNA-seq, and both types of cells were found to express respiratory basal cell lineage markers such as KRT5 and TP63. However, the expression level in bronchial cells is slightly higher. Further studies compared transcriptional changes in nasal or bronchial cells following stimulation with RIG-I ligand SLR14 and found that stimulation with SLR14 resulted in increased expression of antiviral-associated transcripts and was associated with NRF2-mediated oxidative stress.

To investigate whether smoking affects rhinovirus infection, the researchers designed an interesting experiment to expose cells to cigarette smoke by simulating the respiratory environment. The results showed an increase in NRF2 expression in airway epithelial cells in the smoke. And stimulation of cultured bronchial epithelial cells with cigarette smoke extracts also causes an increase in NRF2 levels. The RV1B-infected cells were exposed to cigarette smoke extract, and the expression of IFIT2 $$$ and NQO1$$$ in the cells decreased, and the induction of ISG was decreased, resulting in an increase in viral replication. That is to say, through the oxidative stress of smoke, cells are more susceptible to infection.

Here are two mechanisms by which airway epithelial cells protect against foreign invaders: the antiviral interferon response mechanism and the NRF2-mediated oxidative stress response. In different cell types, the activation effects of these two mechanisms are different. The antiviral interferon mechanism of nasal cells is more than that of bronchial cells, but the oxidative stress response is less.

The results suggest that NRF2-mediated oxidative stress can antagonize the mechanism of antiviral interferon. The researchers believe that there is a delicate balance between different defense mechanisms in the human body. Our respiratory tract can provide protection against other harmful substances during virus invasion. It also provides protection.

If the respiratory tract only encounters a single source of stress, the active defense effect is better, but when two or more stressors are encountered, the defensive effect will be greatly reduced. For example, the smoker may be more easy to catch a cold.

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