Asthma is among the most prevalent chronic inflammatory lung diseases that affects over 5% of the global population. The main causative agents of asthma onset, exacerbation, benicar blood pressure medication and progression include rhinoviruses (RV) and inhaled allergens like house dust mites (HDM). Host cells recognize the ribonucleic acid (RNA) of RV using the endosomal toll-like receptor 3 (TLR) 3, TLR7/8, and cytoplasmic RNA helicases: retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5).
Severe acute respiratory syndrome coronavirus (SARS-CoV-2), the novel coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic, has been shown to cause respiratory illness, however, its role in asthma exacerbations is poorly understood. It is also not clear if preexisting asthma is a risk factor for SARS-CoV-2 infection or severe disease or if it offers protection from the disease.
In a recent study, researchers explored the effects of RV, HDM, and SARS-CoV-2 on differentiated primary human bronchial epithelial cells (HBECs) in vitro and in experimental in vivo RV infection in healthy subjects and asthmatic patients.
Investigations and outcomes
In this pre-print research paper posted to the medRxiv* server, the researchers discussed their investigations of the release of mature Interleukin 1 beta (IL-1b) in differentiated primary human bronchial epithelial cells (HBECs) upon rhinovirus A16 (RV-A16) infection with and without exposure to HDM in a dose and time-dependent manner and noted that there was a formation and activation of inflammasome in the differentiated primary HBECs. Also, the activated inflammasome was enhanced by the exposure to HDM, especially in asthmatic patients with earlier higher pro-IL-1b expression at baseline.
The researchers also found that the pattern recognition receptors (PRR) expressed in the human epithelium acts as a sensor and activator of inflammasome assembly. It was observed that RIG-I inflammasome activation was strongly enhanced in the epithelium of asthmatic patients, primarily in the presence of HDM exposure. However, NLRP3 and MDA5 inflammasomes did not play any role.
The researchers investigated the inflammasome- and IL-1b-mediated immune responses to evaluate the effect of enhanced epithelial RIG-I inflammasome activation on the overall inflammatory responses at the bronchus barrier sites in asthma. The study demonstrated that upon RIG-I inflammasome activation, the immune responses by both inflammasomes- and IL-1b were enhanced in both asthmatic and control patients.
The researchers compared the samples from in vivo RV-A16 infections in asthmatic and control individuals, taken two weeks before infection and four days after infection. It was observed that after rhinovirus infection in vivo, there was a sustained bronchial RIG-I inflammasome activation and inflammasome-mediated immune responses in asthma.
The researchers analyzed the status of antiviral genes and proteins involved with in vivo and in vitro responses to RV-A16 infection. The result depicted rapid virus clearance from healthy individuals; however, it was delayed in patients with asthma which may be due to the decrease in the effectiveness of RIG-I-induced antiviral mechanisms.
They further studied the impact of activation of the RIG-I inflammasome on RIG-I dependent interferon signaling in bronchial epithelium of patients with asthma and found that RIG-I dependent interferon signaling was impaired. Therefore, it can be concluded that viral load can be decreased by timely blocking of the excessive RIG-I inflammasome activation and IL-1b signaling.
Their analysis on the implications of HDM pre-exposure on the timing and strength of antiviral responses suggested that HDM impaired interferon responses in rhinovirus-infected bronchial epithelium of patients with asthma. Lastly, the researchers invest
igated the effect on SARS-CoV-2 infection due to RV-A16-induced RIG-I inflammasome activation and HDM-mediated decrease of IFN responses. It was found that preexisting RV-A16 infection attenuated SARS-CoV-2 replication in asthma.
The study's findings suggested that RV infection and replication activated the RIG-I, but not the NLRP3 inflammasome; RIG-I was further amplified in the presence of HDM. It was also observed that SARS-CoV-2 infection decreased in asthma patients with preexisting RV infection and induction of IFNs in the epithelium, but the RIG-I inflammasome activation and release of proinflammatory mediators increased in the presence of both RV and HDM.
"Timely inhibition of the epithelial RIG-I inflammasome and reduction of IL-1b signaling may lead to more efficient viral clearance and lower the burden of RV and SARS-CoV-2 infection."
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Epithelial RIG-I inflammasome activation suppresses antiviral immunity and promotes inflammatory responses in virus-induced asthma exacerbations and COVID-19. U Radzikowska, A Eljaszewicz, G Tan, N Stocker, A Heider, P Westermann, S Steiner, A Dreher, P Wawrzyniak, B Rückert, J Rodriguez-Coira, D Zhakparov, M Huang, B Jakiela, M Sanak, M Moniuszko, L O’Mahony, T Kebadze, DJ Jackson, MR Edwards, V Thiel, SL Johnston, CA Akdis, M Sokolowska, medRxiv, 2021; Doi: https://doi.org/10.1101/2021.11.16.21266115, https://www.medrxiv.org/content/10.1101/2021.11.16.21266115v1
Posted in: Medical Research News | Medical Condition News | Disease/Infection News
Tags: Actin, Antibody, Asthma, Cell, Chronic, Coronavirus, Coronavirus Disease COVID-19, Gene, Genes, immunity, in vitro, in vivo, Inflammasome, Interferon, Interleukin, Melanoma, Mites, Pandemic, Receptor, Research, Respiratory, Respiratory Illness, Retinoic Acid, Rhinovirus, Ribonucleic Acid, RNA, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Virus, Western Blot
Saurabh Chaturvedi is a freelance writer from Jaipur, India. He is a gold medalist in Masters in Pharmaceutical Chemistry and has extensive experience in medical writing. He is passionate about reading and enjoys watching sci-fi movies.
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