The role of innate immune system in respiratory viral infection related asthma

Abstract

The association between viral infections and asthma has garnered significant attention in recent years. Accumulating evidence suggests that viral infections can trigger asthma exacerbations, while asthma may also influence the susceptibility to viral infections, thereby creating a cycle of worsening symptoms and recurrent asthma attacks. Given that asthma is predominantly driven by Type 2 immune responses and viral infections are typically associated with Type 1 immune responses, the innate immune cells and cytokines that participate in both conditions appear to be the critical bridge connecting these two processes. In particular, innate immune cells play a pivotal role in modulating the immune response at the interface of viral infections and asthma. In this review, we summarize the key innate immune cells and cytokines involved in viral infections and asthma, highlighting their immunoregulatory mechanisms. We aim to provide novel perspectives and potential therapeutic directions for the clinical management of recurrent asthma attacks induced by viral infections.

Keywords: asthma; cytokines; innate immune cells; recurrent asthma attacks; viral infection.

Figure 1

The pathological mechanism of virus infection-induced asthma attack. Epithelial cells infected by viruses secrete CXCL8, which chemoattracts neutrophils to form NETs. This process enhances DCs’ recognition of HDM and promotes IL-4 secretion, driving Th2-mediated type 2 immune responses that may trigger asthma. Viral infection of epithelial cells also leads to the secretion of TSLP and NMU, which chemoattract ILC2 cells and promote the production of type 2 cytokines, while generating memory-like ILC2 cells that increase the capture of allergens and promote the occurrence of asthma. Viral infection of epithelial cells upregulates the expression of ICAM-1, which promotes the adhesion of eosinophils and facilitates the development of asthma. Increased IFN-γ after RV infection can alleviate the onset of asthma symptoms and prevent the occurrence of asthma.

Figure 2

The pathological mechanism of increased susceptibility to viruses after being diagnosed with asthma. In individuals with asthma, genetic variations in the CDHR3 gene drive persistent overexpression of this receptor, thereby enhancing the binding of RV-C to airway epithelial cells and facilitating viral invasion. After infecting epithelial cells, RV-A/B promotes the expression of ICAM, facilitating viral entry; patients with asthma have a deficiency in type I interferon, leading to a reduced type I antiviral response, which increases susceptibility to viruses; TGF maintains lung stability through its powerful anti-inflammatory effects.

Figure 3

The pathological mechanism of the exacerbation of asthma Viral infection after viral infection induces asthma exacerbation. After infecting epithelial cells, viruses attract a large number of eosinophils through the CXCL-9/IP-10 -CXCR3 chemokine axis, which exacerbates asthma. Pre-existing allergic damage induces CUL5 expression, impairing antiviral immunity and promoting neutrophilic inflammation, leading to asthma worsening. NK cells and MDCK cells, following viral infection, respectively suppress asthma exacerbation by promoting antiviral Th1 responses and exerting immunosuppressive effects. Defects in type 1 and 3 interferons also lead to the worsening of asthma symptoms post-viral infection, due to uncontrolled type 2 immunity.