Type III interferons are critical host factors that determine susceptibility to Influenza A viral infection in allergic nasal mucosa
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Summary Background Allergic respiratory conditions have been associated with increased susceptibility to viral infection due to impaired interferon ( IFN )‐related immune responses, but the mechanisms for reinforcement of mucosal immunity against viral infection in allergic diseases are largely unknown. Objectives To determine whether IFN induction would be impaired in allergic nasal mucosa and to identify whether higher loads of influenza A virus ( IAV ) in allergic nasal mucosa could be controlled with IFN treatment. Methods Influenza A virus mRNA , viral titres and IFN expression were compared in IAV ‐infected normal human nasal epithelial ( NHNE , N = 10) and allergic rhinitis nasal epithelial ( ARNE , N = 10) cells. We used in vivo model of allergic rhinitis ( BALB /c mice, N = 10) and human nasal mucosa from healthy volunteers (N = 72) and allergic rhinitis patients (N = 29) to assess the induction of IFN s after IAV infection. Results Influenza A virus mRNA levels and viral titres were significantly higher in ARNE compared with NHNE cells. IFN ‐β and IFN‐λs were induced in NHNE and ARNE cells up to 3 days after IAV infection. Interestingly, induction of IFN ‐λs mRNA levels and the amount of secreted proteins were considerably lower in ARNE cells. The mean IFN ‐λs mRNA level was also significantly lower in the nasal mucosa of AR patients, and we found that recombinant IFN ‐λ treatment attenuated viral mRNA levels and viral titres in IAV ‐infected ARNE cells. In vivo AR mouse exhibited higher viral load after IAV infection, but intranasal inoculation of IFN ‐λ completely decreased IAV protein expression and viral titre in nasal mucosa of IAV ‐infected AR mouse. Conclusion Higher susceptibility of the allergic nasal mucosa to IAV may depend on impairment of type III IFN induction, and type III IFN is a key mechanistic link between higher viral loads and control of IAV infection in allergic nasal mucosa.Keywords:
Viral Shedding
Nasal spray
Route of administration
Olfactory mucosa
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AIM To investigate the curative effects and its mechanism of bencycloquidium on the allergic rhinitis(AR)in rats.METHODS The rat model of allergic rhinitis were induced by ovalbumin(Ova)and Al(OH)_3.Sixty rats were randomly derided into model group,bencycloquidium high medium and low doses groups,beclomethasone group,and vehicle group(each group including 10 rats).After 2 weeks of intranasal administration,the symptoms and morphological features of nasal mucosa of each rat were observed,unilateral nasal secretion of each rat was weighed,and Ova-specific IgE in serum and nasal seretion of each rat were assayed.RESULTS Compared with the vehicle group,the nasal symptoms scale,nasal secretion weight,Ova- specific IgE levels in serum and nasal mucosa,and morphological changes scale of nasal mucosa of rats in the model group were all higher.Compared with the model group,the nasal symptoms of rats in each of the bencycloquidium treament groups showed remarkably relieved(P0.01),morphological changes of nasal mucosa in high and medium doses of bencycloquidium treatment groups appeared to be significantly alleviated (P0.01),Ova-specific IgE in serum and nasal mucosa and nasal secretion of rats in high dose of bencycloquidium treatment group revealed obviously decreased(P0.01).CONCLUSION Bencycloquidium administered intranasally is effective in treating AR,and the mechanism might be through decreasing the Ova- specific IgE.
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Patterns of influenza molecular viral shedding following influenza infection have been well established; predictors of viral shedding however remain uncertain.We sought to determine factors associated with peak molecular viral load, duration of shedding, and viral area under the curve (AUC) in children and adult Hutterite colony members with laboratory-confirmed influenza.A cohort study was conducted in Hutterite colonies in Alberta, Canada. Flocked nasal swabs were collected during three influenza seasons (2007-2008 to 2009-2010) from both symptomatic and asymptomatic individuals infected with influenza. Samples were tested by real-time reverse-transcription polymerase chain reaction for influenza A and influenza B, and the viral load was determined for influenza A-positive samples.For seasonal H1N1, younger age was associated with a larger AUC, female sex was associated with decreased peak viral load and reduced viral shedding duration, while the presence of comorbidity was associated with increased peak viral load. For H3N2, younger age was associated with increased peak viral load and increased AUC. For pandemic H1N1, younger age was associated with increased peak viral load and increased viral AUC, female sex was associated with reduced peak viral load, while inapparent infection was associated with reduced peak viral load, reduced viral shedding duration, and reduced viral AUC.Patterns of molecular viral shedding vary by age, sex, comorbidity, and the presence of symptoms. Predictor variables vary by influenza A subtype.
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Purpose To study the morphological changes of intranasal applications of capsaicin to the rat nasal mucosa. Methods The capsaicin solution of different concentration was applied to the rat nasal cavity for seven days , and the response of the rats was recorded. One week, three weeks and four weeks after the capsaicin applications, the nasal mucosa was taken out and analyzed under optical and electron microscopes. Results It was found that the rats were adapted to capsaicin after three days of the administration. One week after the capsaicin applications, damages of the nasal mucosa were observed. In some regions the cilia were detached from the epithelia. The degree of the mucosa damage was increased with the solution concentration. Four weeks after the capsaicin administration, the ciliated epithelia were restored gradually. Conclusion The damage of the nasal mucosa induced by short-term intranasal administration of capsaicin is reversible. The intranasal application of capsaicin is feasilble , and convenient.
Capsaicin
Olfactory mucosa
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ABSTRACT Background Viral load kinetics and the duration of viral shedding are important determinants for disease transmission. We aim i) to characterize viral load dynamics, duration of viral RNA, and viable virus shedding of SARS-CoV-2 in various body fluids and ii) to compare SARS-CoV-2 viral dynamics with SARS-CoV-1 and MERS-CoV. Methods Medline, EMBASE, Europe PMC, preprint servers and grey literature were searched to retrieve all articles reporting viral dynamics and duration of SARS-CoV-2, SARS-CoV-1 and MERS-CoV shedding. We excluded case reports and case series with < 5 patients, or studies that did not report shedding duration from symptom onset. PROSPERO registration: CRD42020181914. Findings Seventy-nine studies on SARS-CoV-2, 8 on SARS-CoV-1, and 11 on MERS-CoV were included. Mean SARS-CoV-2 RNA shedding duration in upper respiratory tract, lower respiratory tract, stool and serum were 17.0, 14.6, 17.2 and 16.6 days, respectively. Maximum duration of SARS-CoV-2 RNA shedding reported in URT, LRT, stool and serum were 83, 59, 35 and 60 days, respectively. Pooled mean duration of SARS-CoV-2 RNA shedding was positively associated with age (p=0.002), but not gender (p = 0.277). No study to date has cultured live virus beyond day nine of illness despite persistently high viral loads. SARS-CoV-2 viral load in the upper respiratory tract appears to peak in the first week of illness, while SARS-CoV-1 and MERS-CoV peak later. Conclusion Although SARS-CoV-2 RNA shedding in respiratory and stool can be prolonged, duration of viable virus is relatively short-lived. Thus, detection of viral RNA cannot be used to infer infectiousness. High SARS-CoV-2 titers are detectable in the first week of illness with an early peak observed at symptom onset to day 5 of illness. This review underscores the importance of early case finding and isolation, as well as public education on the spectrum of illness. However, given potential delays in the isolation of patients, effective containment of SARS-CoV-2 may be challenging even with an early detection and isolation strategy. Funding No funding was received.
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Respiratory tract
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To study the influence of intranasal medication on the structure, pathology and reversibility of the nasal mucosa to provide a basis for the feasibility of intranasal route of drug administration.Nasal drops of gentamicin were placed in the nasal cavity of rabbits for 3, 5, 7, 14 and 28 days. After that, the drops were stopped and drugs protecting the nasomucosa were used for one and three weeks. After being sacrificed over time, the nasomucosa of the rabbit was observed under optical and electron microscopes.Damage to the nasal mucosa appeared to different extents with prolonged use of nasal drops. Within 3 - 7 days of applying the drug, damages to the nasal mucosa gradually appeared, and after two and four weeks, were most serious. After stopping the drug, the nasal mucosa was gradually restored.Damages of drugs to the nasal mucosa could be restored. The intranasal route of drug administration would be feasible and clinically applicable.
Oral mucosa
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We have previously shown that the intranasal administration of dantrolene ameliorated cognitive dysfunction in the 5XFAD mouse model of Alzheimer's disease. This study examines the morphology of the nasal mucosa after 10 months of intranasal dantrolene in 5XFAD mice.5XFAD mice were either treated with intranasal dantrolene (5 mg/kg, 3 times/wk) from 2 months to 12 months of age or given no treatment at all. The mice were euthanatized at 12 months of age and the snouts were processed for histological examination. The morphology of the nasal mucosa was assessed and compared between the two groups.There were no significant differences in the thickness of the olfactory epithelium or the proportion of the thickness of the glandular layer to the wall of mucosa and submucosa in the nasal passages.Long-term intranasal administration of dantrolene did not significantly change the nasal mucosa morphology in 5XFAD mice.
Olfactory mucosa
Submucosa
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To study the pathological changes and reversibility of the nasal mucosa after drug administration.Gentamicin and insulin were dropped into the nasal cavity of rabbits for 3, 5, 7 days to two weeks, after one and two weeks, the nasal mucosa was taken and observed under optical and electron microscopes.It was found that after 3-7 days of drugs administration, damages of the nasal mucosa gradually appeared, and became most serious after one week when the epithelia in some regions detached from basement membr theane. After stopping drug application, the ciliated epithelia restored quickly and completely, goblet cells reproduced and inflammatory reaction disappeared.The damages induced by drugs on nasal mucosa are reversible. The intranasal route of drug administration is feasible and promising.
Respiratory Mucosa
Drug Administration
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Current investigation aimed to develop a novel Amiloride loaded mucoadhesive nanoemulsion formulation for nose-to-brain delivery. Furthermore, nasal irritation study and histopathological examination of the nasal mucosa were also carried out to assess nonirritant nature of the nanoemulsion. The optimized formulation, surface epithelium lining and the granular cellular structure of the nasal mucosa were totally intact, whereas KCl caused major changes in the ultrastructure of mucosa. Amiloride loaded mucoadhesive nanoemulsion formulations are non toxic on nasal mucosa and can be administered by intranasal route for effective treatment of epilepsy.
Amiloride
Mucoadhesion
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AIM:To study the nasal mucosa and mucociliary toxicity of intranasal administration of diazepam and diazepam compounded with menthol.METHODS:The rabbit nasal mucosa model was established by nasal administration with diazepam and its compound recipe containing menthol for a week.Then we investigated the effects on cellular morphology of the nasal mucosa and its recovery after drug withdrawal.RESULTS:The results of histopathologic slide showed that the thickness of epithelial layers had no obvious change when the rabbit model had been applied with diazepam and its compound recipe for a week.After drug withdrawal,the injury of mucociliary was recovered to some extent.CONCLUSION:Diazepam,menthol and their compound recipe,after intranasal administration,have mild toxicity and the negative effect can be reversible on the nasal mucosa.
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