Rhinovirus inhibits IL-17A and the downstream immune responses in allergic asthma

Abstract

The proinflammatory cytokine interleukin-17A (IL-17A) is known to mediate antimicrobial activity, but its role during rhinovirus (RV) infections and in asthma needs further investigation. Therefore, we addressed the role of IL-17A during allergic asthma and antiviral immune response in human and murine immunocompetent cells. In this study we found that asthmatic children with a RV infection in their upper airways have upregulated mRNA levels of the antiviral cytokine interferon type I (IFN)-β and the transcription factor T-box 21 (TBX21) and reduced levels of IL-17A protein in their peripheral blood mononuclear cells (PBMCs). We also found that IL-17A inhibited RV1b replication in infected human lung epithelial cells A549. Furthermore, by using gene array analysis we discovered that targeted deletion of Il17a in murine lung CD4(+) T cells impaired Oas1g mRNA downstream of Ifnβ, independently from RV infection. Additionally, in PBMCs of children with a RV infection in their nasalpharyngeal fluid OAS1 gene expression was found downregulated. Finally RV1b inhibited IL-17A production in lung CD4(+) T cells in a setting of experimental asthma. These results indicate that the RV1b inhibits IL-17A in T helper type 17 cells and IL-17A clears RV1b infection in epithelial cells. In both cases IL-17A contributes to fend off RV1b infection by inducing genes downstream of interferon type I pathway.

IFN-α/IFN-λ responses to respiratory viruses in paediatric asthma

“…bronchodilators or antihistamines) or a combination of both. The clinical and virology data of the PreDicta cohort in Erlangen were previously described, and will be collectively reported in a manuscript in preparation [16][17][18]. Tables 1 and 2 give an overview of important clinical data of the Erlangen cohorts at the time of recruitment into the PreDicta study.…”

“…Subject recruitment and the timescale of the study are described in detail in the online supplementary material and elsewhere [16]. Some of the clinical aspects of the children are reported in table 1 and were published recently [16][17][18][19].…”

A Testis-Specific Long Non-Coding RNA, lncRNA-Tcam1, Regulates Immune-Related Genes in Mouse Male Germ Cells

“…The physiological significance of some of the target genes in immune defense has been demonstrated by several studies. Interleukin 17a was elevated by infection of rhinovirus in the lung, and led to upregulation of the Oas1g gene, which caused the degradation of viral RNAs ( 64 ). Dengue virus infection in lung epithelial cells upregulated the Ifit3 gene, which suppressed the virus production ( 65 ).…”

Viruses and asthma: the role of common respiratory viruses in asthma and its potential meaning for SARS‐CoV‐2

“…Epithelial cells infected by respiratory viruses such as RV produce inflammatory factors that promote chemotaxis, proliferation and activation of specific immune cells, amplifying in that way inflammatory processes. Although it was previously suggested that RV is not able to infect immune cells, recent studies have argued against this concept, and have demonstrated that RV can infect macrophages, 65 T‐cells 66,67 or mast cells (MCs), which can act as viral reservoirs and release viral particles contributing in that way to viral infection 11 . Due to the proximity of infiltrated inflammatory immune cells with the epithelium from the upper and lower airways, it is reasonable to expect that those cells also have a role in RV infection with a potential impact on asthma initiation or exacerbation.…”