T-helper 2 mechanisms involved in human rhinovirus infections and asthma

Abstract

Human rhinovirus (HRV) is the most common causative agent for the common cold and its respiratory symptoms. For those with asthma, cystic fibrosis, or chronic obstructive pulmonary disease, HRVs can lead to severe and, at times, fatal complications. Furthermore, an array of innate and adaptive host immune responses leads to varying outcomes ranging from subclinical to severe. In this review, we discuss the viral pathogenesis and host immune responses associated with this virus. Specifically, we focus on the immune responses that might skew a T-helper type 2 response, including alarmins, in those with allergic asthma. We also discuss the role of a poor innate immune response with interferons. Finally, we consider therapeutic options for HRV-associated exacerbations of asthma, including biologics and intranasal sprays on the basis of the current literature.

Figure 1.

Rhinoviruses have single-stranded positive sense RNA genomes of ~7200-8500nt in length with structural proteins encoded at the 5’ region and nonstructural at the 3’ end. *Receptor binding region; #Protease.

Figure 2.

Alarmins can activate Type 2 inflammation, causing airway hyperresponsiveness, mucus secretion, bronchoconstriction, and airway remodeling. FeNO: fractional exhaled nitric oxide; IgE: immunoglobulin E; IL: interleukin; ILC2: type2 innate lymphoid cell; Th2: type 2 T helper cell; TSLP: thymic stromal lymphopoietin; #: released from Th2 cells and ILC2. Reproduced with permission of the © ERS 2022: European Respiratory Journal 56 (5) 2000260; DOI: 10.1183/13993003.00260-2020 Published 12 November 2020

Figure 3.

Model for the development of asthma exacerbations with eosinophils acting as antiviral agents, limiting the viral load despite altered innate immunity. IFN: interferon; RIG-I, retinoic acid-inducible gene I; RV: Rhinovirus. Reproduced with permission of the © Annals of Allergy, Asthma, and Immunology 2022: Annals of Allergy, Asthma and Immunology 2022 Apr;128(4):414-422.e2. doi: 10.1016/j.anai.2022.01.007. Epub 2022 Jan 12. PubMed PMID: 35031416.

Figure 4.

Potential effects of anti-alarmin biologics on rhinovirus induced exacerbations of asthma. Reproduced with permission of the © ERS 2022: European Respiratory Journal 56 (5) 2000260; DOI: 10.1183/13993003.00260-2020 Published 12 November 2020