Innate immunity to influenza in chronic airways diseases

Hsu, Alan; See, Hayley; Hansbro, Philip M.; Wark, Peter

doi:10.1111/j.1440-1843.2012.02200.x

Cited by 36 publications

(37 citation statements)

References 128 publications

(227 reference statements)

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“…11 Respiratory viral infections are a major precipitant of exacerbations, with detection rates in exacerbating individuals of up to 78% in asthma, 12 64% in COPD 13 and 46% in cystic fibrosis. 14 In particular, rhinoviruses (RV) are the most common virus type detected during exacerbations.…”

Section: Key Messagesmentioning

confidence: 99%

A novel immunomodulatory function of neutrophils on rhinovirus-activated monocytes in vitro

Tang

Hansbro

Burgess

et al. 2016

Thorax

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BackgroundRhinovirus (RV) infections are the major precipitant of asthma exacerbations. While neutrophilic lung inflammation occurs during such infections, its role remains unclear. Neutrophilic inflammation is associated with increased asthma severity and steroid refractory disease. Neutrophils are vital for controlling infections but also have immunomodulatory functions. Previously, we found that neutrophils respond to viral mimetics but not replication competent RV. We aimed to investigate if neutrophils are activated and/or modulate immune responses of monocytes during RV16 infection.MethodsPrimary human monocytes and autologous neutrophils were cocultured with or without RV16, in direct contact or separated by transwells. RV16-stimulated monocytes were also exposed to lysed neutrophils, neutrophil membrane components or soluble neutrophil intracellular components. Interleukin 6 (IL-6) and C-X-C motif (CXC)L8 mRNA and proteins were measured by quantitative PCR and ELISA at 24 hours.ResultsRV16 induced IL-6 and CXCL8 in monocytes, but not neutrophils. RV16-induced IL-6 and CXCL8 from monocytes was reduced in the presence of live neutrophils. Transwell separation abolished the inhibitory effects. Lysed neutrophils inhibited RV16-induced IL-6 and CXCL8 from monocytes. Neutrophil intracellular components alone effectively inhibited RV16-induced monocyte-derived IL-6 and CXCL8. Neutrophil intracellular components reduced RV16-induced IL-6 and CXCL8 mRNA in monocytes.ConclusionsCell contact between monocytes and neutrophils is required, and preformed neutrophil mediator(s) are likely to be involved in the suppression of cytokine mRNA and protein production. This study demonstrates a novel regulatory function of neutrophils on RV-activated monocytes in vitro, challenging the paradigm that neutrophils are predominantly proinflammatory.

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Section: Key Messagesmentioning

confidence: 99%

A novel immunomodulatory function of neutrophils on rhinovirus-activated monocytes in vitro

Tang

Hansbro

Burgess

et al. 2016

Thorax

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“…Bronchial epithelial cells (BECs) are the primary site of IAV infection, and innate immune responses produced by these cells are important in the early protection against the viruses (1,2). During infection, viral RNAs are recognized by TLR3 and retinoic acid-inducible gene-I (RIG-I).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD

et al. 2017

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“…Cytokine storm is known to be a major factor determining patients’ conditions [30,31], and treatment aimed specifically at modulating the cytokine storm in order to relieve the severity of patients’ conditions has been demonstrated [32]. Thus, we propose that EAex not only directly inhibits virus replication, but also might play a role in modulating immune responses in our animal model.…”

Section: Resultsmentioning

confidence: 99%

Characterization of the Anti-Influenza Activity of the Chinese Herbal Plant Paeonia lactiflora

Chang

Lin

et al. 2014

Viruses

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Bai Shao (BS, the root of Paeonia lactiflora Pall.), a common Chinese herb in many recipes used to treat viral infection and liver diseases, is recognized for its ability to nourish menstruation, its Yin convergence, and as an antiperspirant. However, the mechanism and components for its antiviral function remain to be elucidated. In this study, an ethanolic extract of BS was further partitioned into aqueous and organic parts (EAex) for in vitro functional study and in vivo efficacy testing. EAex exhibited an IC50 of 0.016 ± 0.005 mg/mL against influenza virus A/WSN/33 (H1N1), with broad-spectrum inhibitory activity against different strains of human influenza A viruses, including clinical oseltamivir-resistant isolates and an H1N1pdm strain. The synthesis of both viral RNA and protein was profoundly inhibited when the cells were treated with EAex. A time-of-addition assay demonstrated that EAex exerted its antiviral activity at various stages of the virus replication cycle. We addressed its antiviral activity at virus entry and demonstrated that EAex inhibits viral hemagglutination and viral binding to and penetration into host cells. In vivo animal testing showed that 200 mg/kg/d of EAex offered significant protection against viral infection. We conclude that BS possesses antiviral activity and has the potential for development as an anti-influenza agent.

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Innate immunity to influenza in chronic airways diseases

Cited by 36 publications

References 128 publications

A novel immunomodulatory function of neutrophils on rhinovirus-activated monocytes in vitro

A novel immunomodulatory function of neutrophils on rhinovirus-activated monocytes in vitro

MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD

Characterization of the Anti-Influenza Activity of the Chinese Herbal Plant Paeonia lactiflora

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