Innate immune response to influenza virus

Wu, Shuhua; Metcalf, Jordan P.; Wu, Wenxin

doi:10.1097/qco.0b013e328344c0e3

Cited by 50 publications

(45 citation statements)

References 45 publications

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“…receptors, i.e., endosomal Toll-like receptor 3 (TLR-3) and TLR-7, the cytoplasmic RNA helicase RIG-1, and nucleotide-binding domain-and leucine-rich-repeat-containing proteins (NLRP3) (21,23). NLRP3 senses influenza viruses through an M2 ion channel as well as M2-mediated perturbation of ionic concentrations or viral RNA (21,(24)(25)(26)(27)(28) and can be activated to recruit caspase-1 to the inflammasome, which in turn cleaves immature cytokines such as pro-IL-1␤ and pro-IL-18, resulting in their secretion into the extracellular space (21,(28)(29)(30). In our study, we found that inflammasome responses were elicited in mice after virus infection and that the low-dose repeated-infection groups had greater inflammasome responses, as indicated by increased IL-1␤ and IL-18 concentrations in lung tissues and BALF (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that the NLRP3 inflammasome response is activated during influenza virus infection, causing increased secretion of the proinflammatory cytokines IL-1␤ and IL-18 (21). To define the relationship of the inflammasome response to the virus dose used for challenge, we measured levels of IL-1␤ and IL-18 expression in lung tissues 5 days after single or repeated challenges with different doses of A/PR/8 virus.…”

Section: Repeated Low-dose Infection With Influenza Virus Causes Earlmentioning

confidence: 99%

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Repeated Low-Dose Influenza Virus Infection Causes Severe Disease in Mice: a Model for Vaccine Evaluation

Song

Wang

Zhang

et al. 2015

J Virol

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Influenza infection causes severe disease and death in humans. In traditional vaccine research and development, a single highdose virus challenge of animals is used to evaluate vaccine efficacy. This type of challenge model may have limitations. In the present study, we developed a novel challenge model by infecting mice repeatedly in short intervals with low doses of influenza A virus. Our results show that compared to a single high-dose infection, mice that received repeated low-dose challenges showed earlier morbidity and mortality and more severe disease. They developed higher vial loads, more severe lung pathology, and greater inflammatory responses and generated only limited influenza A virus-specific B and T cell responses. A commercial trivalent influenza vaccine protected mice against a single high and lethal dose of influenza A virus but was ineffective against repeated low-dose virus challenges. Overall, our data show that the repeated low-dose influenza A virus infection mouse model is more stringent and may thus be more suitable to select for highly efficacious influenza vaccines. IMPORTANCEInfluenza epidemics and pandemics pose serious threats to public health. Animal models are crucial for evaluating the efficacy of influenza vaccines. Traditional models based on a single high-dose virus challenge may have limitations. Here, we describe a new mouse model based on repeated low-dose influenza A virus challenges given within a short period. Repeated low-dose challenges caused more severe disease in mice, associated with higher viral loads and increased lung inflammation and reduced influenza A virus-specific B and T cell responses. A commercial influenza vaccine that was shown to protect mice from high-dose challenge was ineffective against repeated low-dose challenges. Overall, our results show that the low-dose repeated-challenge model is more stringent and may therefore be better suited for preclinical vaccine efficacy studies. Influenza viruses, through annual outbreaks and occasional pandemics, pose a significant threat to public health. Each year, influenza causes the hospitalization of millions of people and is linked to ϳ250,000 to 500,000 deaths worldwide (1). Influenza virus infection causes acute respiratory disease in humans and the sudden onset several symptoms, such as high fever, coryza, cough, headache, prostration, malaise, and inflammation of the upper respiratory tree and trachea, which can progress to pneumonia (2-4).Vaccines can prevent influenza virus infections (5, 6). They are relatively ineffective at protecting highly vulnerable populations such as immunocompromised or aged individuals. They also perform poorly in years when the vaccine strains are mismatched to the circulating strains. A universal vaccine against all subtypes and strains of influenza virus would provide broader protection, but such constructs are not yet commercially available (7-10).Novel vaccines, prior to their testing in humans, are evaluated in experimental animal models, which have limitations...

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Section: Discussionmentioning

confidence: 99%

Section: Repeated Low-dose Infection With Influenza Virus Causes Earlmentioning

confidence: 99%

Repeated Low-Dose Influenza Virus Infection Causes Severe Disease in Mice: a Model for Vaccine Evaluation

Song

Wang

Zhang

et al. 2015

J Virol

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“…The ever growing family of the PRRs now includes three main types: the Toll like receptors (TLRs), retinoic acid inducible gene 1 protein (RIG-1)-like helicases (RLRs) and nucleotide binding domain and leucine-rich-repeatcontaining proteins (NLRs) [23]. It is now fully recognized that they play an essential role in many cell functions, including neutrophil biology.…”

Section: Neutrophil Receptor Signalling Pathways In Agingmentioning

confidence: 99%

“…They are able to modulate various responses to viruses. The response can be a pro-inflammatory response or a direct antiviral response but both types are mediated by the inflammasome [23]. The inflammasome is a complex of molecules activated by specific PRRs (NLRs and AIM2) and responds specifically to an aggression via the activation of inflammatory caspases such as caspase-1 and caspase-5, resulting ultimately in the production of a wide range of cytokines [32].…”

Section: Neutrophil Receptor Signalling Pathways In Agingmentioning

confidence: 99%

“…In the case of influenza infection which is known to be devastating in elderly because of the decreased immune response, more data are emerging suggesting that the increased susceptibility of the elderly is due in large part to the alterations in the innate immune response [23,61,68,69]. More specifically the TLR responses in DCs may be predictive of the efficacy of the influenza vaccine.…”

Section: Dendritic Cell Functional Changes With Agingmentioning

confidence: 99%

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The Innate Immune System and Aging: What is the Contribution to Immunosenescence ?

Fülöp

Fortin²,

Lesur³

et al. 2012

TOLSJ

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Abstract:The immune system plays an important role in the defence against various threats to health, such as pathogens, cancer cells or modified-self proteins. With aging there is a decrease in the immune response, called immunosenescence, concomitantly with the increase in some age-related diseases such as infections, autoimmune disorders, chronic inflammatory diseases and cancer. The immune response is traditionally divided between innate and adaptive immune responses. Accumulating evidence suggests that immunosenescence is not only restricted to the adaptive but also affects the innate immune system. Assessment of innate immune system functions revealed that it is also susceptible to age-related dysregulation. Furthermore, it is becoming clear that the sustained function of innate cells is indispensable for the adequate functioning of the adaptive immune response. This review will describe the changes in the innate immune response with aging and the recent discoveries, which may shed new light on its contribution to immunosenescence.

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Multiple modes of action of myricetin in influenza A virus infection

Sang

Huang

Tian

et al. 2021

Phytotherapy Research

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Influenza A virus remains a major threat to public health worldwide after its first pandemic. Scientists keep searching novel anti-influenza drugs, of which natural products present to be an important source. Myricetin, a natural flavonol compound, which exists in many edible plants, which has a wide range of biological activities, but its anti-influenza A virus activity is ambiguous. This study aims to evaluate the antiinfluenza activity of myricetin and elucidate its underlying mechanism. Our results demonstrated that myricetin could significantly inhibit influenza A virus replication, reduce viral polymerase activity via selective inhibition of viral PB2 subunit, and the production of inflammatory cytokines by inhibiting TLR3 signaling pathway. The binding affinity analysis and the result of molecular docking revealed that myricetin interacted with the PB2 cap-binding pocket of influenza A virus. The above results suggested myricetin could exhibit anti-influenza virus activity with low cytotoxicity as well, and myricetin had low toxicity in BALB/c mice in vivo. Results from this study highlighted myricetin could be considered as a promising anti-influenza virus agent with dual inhibition profile. Furthermore, the compound with similar structure would provide a new option for the development of novel inhibitors against influenza A virus.

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Innate immune response to influenza virus

Cited by 50 publications

References 45 publications

Repeated Low-Dose Influenza Virus Infection Causes Severe Disease in Mice: a Model for Vaccine Evaluation

Repeated Low-Dose Influenza Virus Infection Causes Severe Disease in Mice: a Model for Vaccine Evaluation

The Innate Immune System and Aging: What is the Contribution to Immunosenescence ?

Multiple modes of action of myricetin in influenza A virus infection

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