Pattern recognition receptor immunomodulation of innate immunity as a strategy to limit the impact of influenza virus

Pizzolla, Angela; Smith, Jeffrey M.; Brööks, Andrëw G.; Reading, Patrick C.

doi:10.1189/jlb.4mr0716-290r

Cited by 23 publications

(15 citation statements)

References 117 publications

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“…The results of this study expand our understanding of Lp-mediated cross-protection at the respiratory mucosa and emphasize the role of Lp as a local immunomodulatory mediator. As of this writing, there are numerous examples of cross-protection achieved with live bacteria, inactivated bacteria, bacterial components, and bacterial PRR ligands used to combat respiratory virus infections (reviewed in [34,35]). A wide variety of both complementary and distinct mechanisms have been implicated, which may relate in part to differences in bacterial species, strains, and preparations used and the complexities introduced by differences in target virus pathogens.…”

Section: Results and Dicussionmentioning

confidence: 99%

Administration of immunobiotic Lactobacillus plantarum delays but does not prevent lethal pneumovirus infection in Rag1−/− mice

Percopo

Rosenberg

2017

Journal of Leukocyte Biology

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Administration of immunobiotic (Lp) directly to the respiratory mucosa promotes cross-protection against lethal pneumovirus infection via B-cell-independent mechanisms. In this study, we examined Lp-mediated cross protection in mice which cannot clear virus from lung tissue. Although Lp was initially protective, mice ultimately succumbed to a delayed lethal outcome associated with local production of the proinflammatory cytokines CCL1, -2, and -7, granulocyte recruitment, and ongoing virus replication. By contrast, CD8 mice, which are fully capable of clearing virus, are protected by Lp with no delayed lethal outcome, granulocyte recruitment to the airways, or induction of CCL7. Repeated administration of Lp to virus-infected mice had no impact on delayed mortality. Moreover, administration of Lp to the respiratory mucosa resulted in no induction of IFN-α or -β in or wild-type mice, and IFNR gene deletion had no impact on Lp-mediated protection. Overall, our findings indicate that although Lp administered to the respiratory tract has substantial impact on lethal virus-induced inflammation in situ, endogenous virus clearance mechanisms are needed to promote sustained protection. Our results suggest that a larger understanding of the mechanisms and mediators that limit acute virus-induced inflammation may yield new and useful therapeutic modalities.

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Section: Results and Dicussionmentioning

confidence: 99%

Administration of immunobiotic Lactobacillus plantarum delays but does not prevent lethal pneumovirus infection in Rag1−/− mice

Percopo

Rosenberg

2017

Journal of Leukocyte Biology

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“…Among the diversified antiviral strategies developed to counteract the different steps of the viral life cycle (30)(31)(32)(33)(34), interfering with the initial phases of infection, such as the viral evasion of the IFN system, is an attractive therapeutic approach against several types of viruses (35)(36)(37)(38). Since EBOV inhibition of the IFN response massively contributes to viral pathogenesis (4, 5), restoring the IFN system could represent a promising strategy for EBOV control (13).…”

Section: Discussionmentioning

confidence: 99%

Quercetin Blocks Ebola Virus Infection by Counteracting the VP24 Interferon-Inhibitory Function

Fanunza

Iampietro

Distinto

et al. 2020

Antimicrob Agents Chemother

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Ebola virus (EBOV) is among the most devastating pathogens causing fatal hemorrhagic fever in humans. The epidemics from 2013 to 2016 resulted in more than 11,000 deaths, and another outbreak is currently ongoing. Since there is no FDA-approved drug so far to fight EBOV infection, there is an urgent need to focus on drug discovery. Considering the tight correlation between the high EBOV virulence and its ability to suppress the type I interferon (IFN-I) system, identifying molecules targeting viral protein VP24, one of the main virulence determinants blocking the IFN response, is a promising novel anti-EBOV therapy approach. Hence, in the effort to find novel EBOV inhibitors, a screening of a small set of flavonoids was performed; it showed that quercetin and wogonin can suppress the VP24 effect on IFN-I signaling inhibition. The mechanism of action of the most active compound, quercetin, showing a half-maximal inhibitory concentration (IC50) of 7.4 μM, was characterized to significantly restore the IFN-I signaling cascade, blocked by VP24, by directly interfering with the VP24 binding to karyopherin-α and thus restoring P-STAT1 nuclear transport and IFN gene transcription. Quercetin significantly blocked viral infection, specifically targeting EBOV VP24 anti-IFN-I function. Overall, quercetin is the first identified inhibitor of the EBOV VP24 anti-IFN function, representing a molecule interacting with a viral binding site that is very promising for further drug development aiming to block EBOV infection at the early steps.

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“…Innate immune cells can recognize influenza A viruses and their infected cells by toll-like receptors (TLRs) [124]. This recognition can lead to the induction of an inflammatory response that, in turn, controls the replication and spread of the virus [31].…”

Section: Ifns and Energy Metabolismmentioning

confidence: 99%

Metabolic host response and therapeutic approaches to influenza infection

et al. 2020

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Based on available metabolomic studies, influenza infection affects a variety of cellular metabolic pathways to ensure an optimal environment for its replication and production of viral particles. Following infection, glucose uptake and aerobic glycolysis increase in infected cells continually, which results in higher glucose consumption. The pentose phosphate shunt, as another glucose-consuming pathway, is enhanced by influenza infection to help produce more nucleotides, especially ATP. Regarding lipid species, following infection, levels of triglycerides, phospholipids, and several lipid derivatives undergo perturbations, some of which are associated with inflammatory responses. Also, mitochondrial fatty acid βoxidation decreases significantly simultaneously with an increase in biosynthesis of fatty acids and membrane lipids. Moreover, essential amino acids are demonstrated to decline in infected tissues due to the production of large amounts of viral and cellular proteins. Immune responses against influenza infection, on the other hand, could significantly affect metabolic pathways. Mainly, interferon (IFN) production following viral infection affects cell function via alteration in amino acid synthesis, membrane composition, and lipid metabolism. Understanding metabolic alterations required for influenza virus replication has revealed novel therapeutic methods based on targeted inhibition of these cellular metabolic pathways.

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Pattern recognition receptor immunomodulation of innate immunity as a strategy to limit the impact of influenza virus

Cited by 23 publications

References 117 publications

Administration of immunobiotic Lactobacillus plantarum delays but does not prevent lethal pneumovirus infection in Rag1−/− mice

Administration of immunobiotic Lactobacillus plantarum delays but does not prevent lethal pneumovirus infection in Rag1−/− mice

Quercetin Blocks Ebola Virus Infection by Counteracting the VP24 Interferon-Inhibitory Function

Metabolic host response and therapeutic approaches to influenza infection

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