This study was carried out to determine whether Tollip downregulates ST2 signaling via inhibition of IRAK1, but promotes soluble ST2 (sST2) production, thereby limiting excessive IL-8 production in human airway epithelial cells during RV infection in a type 2 cytokine milieu (e.g., IL-13 and IL-33 stimulation).
These observations suggested that the former ILC/DC profiles could be a predictor of a balanced cellular and humoral immune outcome.In addition, following i.n. delivery Rhinovirus (RV) and Adenovius type 5 (Ad5) vectors that induced elevated ILC2-derived IL-13, NKp46<sup>+</sup> ILC1/ILC3-derived-IFN-γ and no IL-17A, predominantly recruited CD11b<sup>-</sup> B220<sup>+</sup> plasmacytoid DCs (pDC).
Genetic defects in several pattern recognition receptors include MDA5 deficiency, which impairs viral RNA sensing and confers human rhinovirus susceptibility; RNA polymerase III haploinsufficiency, which impairs sensing of A:T-rich virus DNA and confers VZV susceptibility; and TLR3 deficiency, which causes HSV-1 encephalitis (HSE) or influenza virus pneumonitis.
CDHR3 (cadherin-related family member 3) is a transmembrane protein that is highly expressed in airway epithelia and the only known receptor for rhinovirus C (RV-C).
Lower epithelial IFN-α/β expression was related to greater viral load, worse airway symptoms, airway hyperresponsiveness, and reductions in lung function during rhinovirus infection.
In adjusted analysis, rhinovirus C infections were associated with increased IFN-α (<i>P</i> = 0.045) and decreased RORC2 expression (<i>P</i> = 0.025).
Pre-treatment of A549 respiratory epithelial cells with a physiological concentration (10<sup>-7</sup>M) of 25(OH)D induced transient resistance to infection with RV-16 and attenuated RV-16-induced expression of the genes encoding intercellular adhesion molecule 1 (ICAM-1, a cell surface glycoprotein that acts as the cellular receptor for major group rhinoviruses) and platelet-activating factor receptor (PAFR, a G-protein coupled receptor implicated in adhesion of Streptococcus pneumoniae to respiratory epithelial cells).
Here, we studied the impact of a small-molecule inhibitor (MEKi) on the IFN response following challenge with two major respiratory viruses rhinovirus (RV2) and respiratory syncytial virus (RSVA2) and a TLR3 agonist, poly(I:C).
In adjusted analysis, rhinovirus C infections were associated with increased IFN-α (<i>P</i> = 0.045) and decreased RORC2 expression (<i>P</i> = 0.025).
Lower epithelial IFN-α/β expression was related to greater viral load, worse airway symptoms, airway hyperresponsiveness, and reductions in lung function during rhinovirus infection.
In contrast, pretreatment with CO did not increase DNA fragmentation and did not reduce the expression of intercellular adhesion molecule-1, the RV14 receptor, or the number of acidic endosomes, through which RV RNA enters the cytoplasm.
Small interfering RNA-mediated knockdown of DUSP10 identified a role for the protein in negatively regulating inflammatory cytokine production in response to interleukin-1β (IL-1β), alone and in combination with RV, without any effect on RV replication.
Naive and house dust mite-treated NLRP3-/- and IL-1β-/- mice, as well as IL-1 receptor antagonist-treated mice, showed attenuated airway inflammation and responsiveness following RV infection.
The inflammasome-mediated IL-1β secretion and pyroptosis in human nasal epithelial progenitor cells and hNECs on hRV infection were dependent on the DDX33/DDX58-NLRP3-caspase-1-GSDMD axis.
Infants with rhinovirus had higher levels of NFκB-induced type-2 cytokines (IL-10 and IL-13; FDR<0.01).ConclusionIn infants with bronchiolitis, rhinovirus and RSV infections had different nasal airway microRNA profiles associated with NFκB signaling.
Genotyping of 41 chimpanzees and examination of 24 published chimpanzee genomes from subspecies across Africa showed universal homozygosity for the cadherin-related family member 3CDHR3-Y<sub>529</sub> allele, which increases risk for rhinovirus C infection and asthma in human children.
The increase of Th2-related cytokines, especially IL-5 and IL-13, is a relevant biomarker for RV infection in asthmatic children with severe exacerbation.