Respiratory syncytial virus increases eosinophil extracellular traps in a murine model of asthma

Abstract

BackgroundRespiratory viral infections are the leading cause of asthma exacerbations. Eosinophil activation results in the formation of eosinophil extracellular traps (EETs), which release web-like structures of DNA and proteins that bind, disarm and extracellularly kill pathogens.ObjectiveWe investigated whether the respiratory syncytial virus (RSV) in vitro could induce EETs in bronchoalveolar lavage fluid eosinophils in a murine model of asthma.MethodsBALB/cJ mice (6–8 weeks old) were sensitized with 2 subcutaneous injections of ovalbumin (20 μg) on days 0 and 7, followed by three intranasal challenges with ovalbumin (100 μg) on days 14, 15, and 16 of the protocol. The control group received Dulbecco's phosphate-buffered saline. Bronchoalveolar lavage fluid eosinophils of ovalbumin group or control group were stimulated with RSV (103 PFU/mL) in vitro for 3 hours. After that, culture supernatant was collected to perform the analyses proposed in this study.ResultsWe verified an increase in extracellular DNA concentration in bronchoalveolar lavage fluid eosinophils from ovalbumin group stimulated with RSV (103 PFU/mL) in vitro, which was confirmed by confocal microscopy. We demonstrated that most cells are negative for annexin V and propidium iodide in all groups evaluated. Also, RSV in vitro decreased interferon-ɣ in culture supernatant when compared to the ovalbumin group.ConclusionIn this study, we demonstrated for the first time that RSV in vitro induces EETs formation in eosinophils from asthmatic mice.

Eosinophil responses during COVID-19 infections and coronavirus vaccination

“…24,25 Both human and murine eosinophils produce NO via inducible NO synthase, which can have direct antiviral effects on parainfluenza virus and RSV. 23,26,27 Eosinophils are able to produce extracellular traps composed of eosinophilic granule proteins bound to genomic and mitochondrial DNA, and murine eosinophils can release these DNA traps in response to RSV infection in vitro, 28 especially in oxidative lung tissue environments. 29 Eosinophils are also capable of quickly mobilizing preformed granule pools of T H 1 cytokines, including IL-12 and IFN-g, which are important for mounting effective antiviral immune responses.…”

Innate Immune Components That Regulate the Pathogenesis and Resolution of hRSV and hMPV Infections

“…Moreover, eosinophils are capable of forming eosinophil extracellular traps (EETs), which are similar to NETs and are characterized by the catapulting of mitochondrial DNA in association with antimicrobial proteins [ 203 ]. EETs have been shown to occur during a hRSV infection of eosinophils in vitro [ 204 ] and probably promote airway obstruction, which could aggravate hRSV infection symptoms and may lead to the long-term development of asthma.…”

“NETs and EETs, a Whole Web of Mess”

“…This study revealed that eosinophils could act directly against influenza A, but they also mediated CD8+ T cell responses against the virus [182]. Similarly, respiratory syncytial virus (RSV) also induces EET formation in vitro in a concentration-dependent manner [181]. Interestingly, RSV is frequently related to asthma [185] exacerbations, further implicating a role for eosinophils in these infections.…”

“…Eosinophils also play a role in many viral infections [181][182][183]. A study was completed looking at how eosinophils respond to influenza A virus infection [184].…”

“…Interestingly, RSV is frequently related to asthma [185] exacerbations, further implicating a role for eosinophils in these infections. RSV induces EETs in the bronchoalveolar lavage fluid in mice with asthma which is suggested to promote airway obstruction, mucus plugs, and inflammation in respiratory airways [181].…”