Rhinovirus Suppresses TGF-β-GARP Presentation by Peripheral NK Cells

Abstract

Asthma is a chronic airway disease whose exacerbations are often triggered by rhinovirus infection. TGF-β1 induces rhinovirus replication in infected cells. Moreover, TGF-β1 is a pleiotropic mediator that is produced by many immune cells in the latent, inactive form bound to the latency-associated peptide (LAP) and to the transmembrane protein glycoprotein A repetitions predominant (GARP). In this study we wanted to investigate the effect of rhinovirus infection on the TGF-β secretion and the downstream signaling via TGF-βRI/RII in peripheral blood mononuclear cells from control and asthmatic patients after rhinovirus infection ex vivo. Here, we found a significant upregulation of TGF-βRII in untouched PBMCs of asthmatics as well as a suppression of TGF-β release in the rhinovirus-infected PBMC condition. Moreover, consistent with an effect of TGF-β on Tregs, PBMCs infected with RV induced Tregs, and TGF-βRII directly correlated with RV1b mRNA. Finally, we found via flow cytometry that NK cells expressed less GARP surface-bound TGF-β, while cytokine-producing NKbright cells were induced. In summary, we show that rhinovirus infection inhibits TGF-β release in PBMCs, which results in the activation of both Treg and NK cells.

Elevated CD56brightNK cell and IFNγ levels in the blood of children with common cold provides a clue for preventing COVID-19

“…In line with the elevated levels of IFNγ in the blood, we observed a signi cantly higher proportion of CD56 bright NK cells in the blood of children with colds compared to healthy children. This is a novel nding, as previous studies only reported an upregulation of CD56 bright NK cell subset in the blood of asthmatic individuals and healthy adults infected with rhinovirus [35]. CD56 bright NK cells primarily exert antiviral effects through the secretion of in ammatory cytokines such as IFNγ and TNFα [17].…”

Poly I:C Pre-Treatment Induced the Anti-Viral Interferon Response in Airway Epithelial Cells

“…Respiratory viruses primarily infect airway epithelial cells, which are the first defense barrier of the airway mucosa [15][16][17][18][19]. The host responds to viral infections by releasing antiviral factors like interferon type I (interferon α), II (interferon γ), and III (interferon λ) [20][21][22][23], leading to cell death of infected cells. As a result, during repeated infections there is a disruption of the epithelial barrier with increased risk of virus dissemination to other distant sites through the sub-epithelial tissue to encounter the peripheral blood immune cells [24][25][26][27], this happens especially in the epithelium of asthmatic patients, since the epithelial integrity is already impaired [28][29][30].…”