The Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice

Simpson, Jennifer; Lynch, Jason P.; Loh, Zhixuan; Zhang, Vivian; Werder, Rhiannon B.; Spann, Kirsten; Phipps, Simon

doi:10.1038/s41598-017-02564-9

Cited by 12 publications

(12 citation statements)

References 71 publications

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“…115 Also, IFN-b has immune-modulating properties and can inhibit eosinophilic asthma-like pathophysiology in pneumovirus-infected mice. 116 Overall, RSV-induced bronchiolitis typically affects neonates at the critical time window of lung development and therefore might have long-term influences. Murine models have shown that RSV infection causes more lung damage during the proliferative stage of lung growth compared with the equilibrated stage.…”

Section: Rsv-induced Wheezing and Asthmamentioning

confidence: 99%

Role of viral infections in the development and exacerbation of asthma in children

Jartti

Gern

2017

Journal of Allergy and Clinical Immunology

372

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Viral infections are closely linked to wheezing illnesses in children of all ages. Respiratory syncytial virus (RSV) is the main causative agent of bronchiolitis, whereas rhinovirus (RV) is most commonly detected in wheezing children thereafter. Severe respiratory illness induced by either of these viruses is associated with subsequent development of asthma, and the risk is greatest for young children who wheeze with RV infections. Whether viral illnesses actually cause asthma is the subject of intense debate. RSV-induced wheezing illnesses during infancy influence respiratory health for years. There is definitive evidence that RSV-induced bronchiolitis can damage the airways to promote airway obstruction and recurrent wheezing. RV likely causes less structural damage and yet is a significant contributor to wheezing illnesses in young children and in the context of asthma. For both viruses, interactions between viral virulence factors, personal risk factors (eg, genetics), and environmental exposures (eg, airway microbiome) promote more severe wheezing illnesses and the risk for progression to asthma. In addition, allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. Treatments that inhibit inflammation have efficacy for RV-induced wheezing, whereas the anti-RSV mAb palivizumab decreases the risk of severe RSV-induced illness and subsequent recurrent wheeze. Developing a greater understanding of personal and environmental factors that promote more severe viral illnesses might lead to new strategies for the prevention of viral wheezing illnesses and perhaps reduce the subsequent risk for asthma.

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Section: Rsv-induced Wheezing and Asthmamentioning

confidence: 99%

Role of viral infections in the development and exacerbation of asthma in children

Jartti

Gern

2017

Journal of Allergy and Clinical Immunology

372

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“…IPS-1-deficient (IPS-1 −/− ) mice show severe defects in both RIG-I and MDA5 mediated induction of type I IFNs and inflammatory cytokines and were susceptible to RNA virus infection [ 174 ]. Furthermore, IPS-1 −/− mice are more susceptible to acute infection with pneumonia virus of mice (PVM) and WNV [ 176 , 177 ]. Additional studies suggest that IPS-1 signaling contributes to the recruitment of pDCs and type I IFN production, which plays a critical role in effective antiviral responses [ 176 , 177 , 178 ].…”

Section: Rig-i Like Receptors (Rlrs)mentioning

confidence: 99%

Innate Immune Sensing of Viruses and Its Consequences for the Central Nervous System

Singh

Koury

Kaul

2021

Viruses

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Viral infections remain a global public health concern and cause a severe societal and economic burden. At the organismal level, the innate immune system is essential for the detection of viruses and constitutes the first line of defense. Viral components are sensed by host pattern recognition receptors (PRRs). PRRs can be further classified based on their localization into Toll-like receptors (TLRs), C-type lectin receptors (CLR), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), NOD-like receptors (NLRs) and cytosolic DNA sensors (CDS). TLR and RLR signaling results in production of type I interferons (IFNα and -β) and pro-inflammatory cytokines in a cell-specific manner, whereas NLR signaling leads to the production of interleukin-1 family proteins. On the other hand, CLRs are capable of sensing glycans present in viral pathogens, which can induce phagocytic, endocytic, antimicrobial, and pro- inflammatory responses. Peripheral immune sensing of viruses and the ensuing cytokine response can significantly affect the central nervous system (CNS). But viruses can also directly enter the CNS via a multitude of routes, such as the nasal epithelium, along nerve fibers connecting to the periphery and as cargo of infiltrating infected cells passing through the blood brain barrier, triggering innate immune sensing and cytokine responses directly in the CNS. Here, we review mechanisms of viral immune sensing and currently recognized consequences for the CNS of innate immune responses to viruses.

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“…Asthma is a polygenic disorder, underpinned by gene-environment interactions. As individual SNP effects on disease risk are small, we elected to use knockout mice, which we have used previously to identify novel pathogenic mechanisms [34,37,47]. We believe this approach is preferable to using an extremely high inoculum in WT mice that can induce non-physiological responses and increase the potential for false positives.…”

Section: Plos Pathogensmentioning

confidence: 99%

HMGB1 amplifies ILC2-induced type-2 inflammation and airway smooth muscle remodelling

et al. 2020

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Type-2 immunity elicits tissue repair and homeostasis, however dysregulated type-2 responses cause aberrant tissue remodelling, as observed in asthma. Severe respiratory viral infections in infancy predispose to later asthma, however, the processes that mediate tissue damage-induced type-2 inflammation and the origins of airway remodelling remain illdefined. Here, using a preclinical mouse model of viral bronchiolitis, we find that increased epithelial and mesenchymal high-mobility group box 1 (HMGB1) expression is associated with increased numbers of IL-13-producing type-2 innate lymphoid cell (ILC2s) and the expansion of the airway smooth muscle (ASM) layer. Anti-HMGB1 ablated lung ILC2 numbers and ASM growth in vivo, and inhibited ILC2-mediated ASM cell proliferation in a co-culture model. Furthermore, we identified that HMGB1/RAGE (receptor for advanced glycation endproducts) signalling mediates an ILC2-intrinsic IL-13 auto-amplification loop. In summary, therapeutic targeting of the HMGB1/RAGE signalling axis may act as a novel asthma preventative by dampening ILC2-mediated type-2 inflammation and associated ASM remodelling.

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The Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice

Cited by 12 publications

References 71 publications

Role of viral infections in the development and exacerbation of asthma in children

Role of viral infections in the development and exacerbation of asthma in children

Innate Immune Sensing of Viruses and Its Consequences for the Central Nervous System

HMGB1 amplifies ILC2-induced type-2 inflammation and airway smooth muscle remodelling

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