The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response

Journal for ImmunoTherapy of Cancer, Journal Year: 2020, Volume and Issue: 8(1), P. e000930 - e000930

Published: May 1, 2020

The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around world. In patients who experience severe disease, acute respiratory distress is often accompanied a pathological immune reaction, sometimes referred to as ‘cytokine storm’. One hallmark feature of profound inflammatory state seen in with COVID-19 succumb pneumonia and hypoxia marked elevation serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), 8 (IL-8) 6 (IL-6). Initial from outbreaks Italy, China USA anecdotally demonstrated improved outcomes for critically ill administration cytokine-modulatory therapies, anti-IL-6 agents. Although ongoing trials are investigating access these therapies concern, numbers cases worldwide continue climb. An immunology-informed approach may help identify alternative agents modulate inflammation COVID-19. Drawing extensive administering other immune-modulating Society Immunotherapy Cancer offers this perspective potential alternatives that also warrant consideration management systemic response pulmonary compromise can be

Language: Английский

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Poxviruses and the immune system: Implications for monkeypox virus

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 113, P. 109364 - 109364

Published: Oct. 22, 2022

Language: Английский

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Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 13, 2024

Introduction Global microplastic (MP) pollution is now well recognized, with humans and animals consuming inhaling MPs on a daily basis, growing body of concern surrounding the potential impacts human health. Methods Using mouse model mild COVID-19, we describe herein effects azide-free 1 μm polystyrene MP beads, co-delivered into lungs SARS-CoV-2 omicron BA.5 inoculum. The effect host response to infection was analysed using histopathology RNA-Seq at 2 6 days post-infection (dpi). Results Although reduced clearance from lung, virus titres viral RNA levels were not significantly affected by MPs, overt MP-associated clinical or histopathological changes observed. However, infected revealed that exposure suppressed innate immune responses dpi increased pro-inflammatory signatures dpi. cytokine profile showed significant correlation ‘cytokine release syndrome’ signature observed in some COVID-19 patients. Discussion findings are consistent recent finding can inhibit phagocytosis apoptotic cells via binding Tim4. They also add literature suggesting dysregulate inflammatory processes specific disease settings.

Language: Английский

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Current Insights in Genetics of Sarcoidosis: Functional and Clinical Impacts

Journal of Clinical Medicine, Journal Year: 2020, Volume and Issue: 9(8), P. 2633 - 2633

Published: Aug. 13, 2020

Sarcoidosis is a complex disease that belongs to the vast group of autoinflammatory disorders, but etiological mechanisms which are not known. At crosstalk environmental, infectious, and genetic factors, sarcoidosis multifactorial requires multidisciplinary approach for research, in particular, next generation sequencing (NGS) tools, has made it possible identify new pathways propose mechanistic hypotheses. Codified treatments cannot always respond most progressive forms identification metabolic tracks challenge future management severe patients. Here, we review current knowledge regarding genes identified by both genome wide association studies (GWAS) whole exome (WES), as well connection these with research on immune-related disorders.

Language: Английский

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Severe COVID-19 Patients Show an Increase in Soluble TNFR1 and ADAM17, with a Relationship to Mortality

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(16), P. 8423 - 8423

Published: Aug. 5, 2021

Overproduction of inflammatory cytokines is a keystone event in COVID-19 pathogenesis; TNF and its receptors (TNFR1 TNFR2) are critical pro-inflammatory molecules. ADAM17 releases the soluble (sol) forms TNF, TNFR1, TNFR2. This study evaluated TNFRs, at protein, transcriptional, gene levels patients with different disease severity. In total, 102 were divided into mild, moderate, severe condition groups. A group healthy donors (HD; n = 25) was included. Our data showed that solTNFR1 solTNFR2 elevated among (p < 0.0001), without increasing transcriptional level. Only higher as compared to mildly ill 0.01), level who died than those survived 0.0001). The had discrete negative correlation C-reactive protein 0.006, Rho −0.33). solADAM17 mild conditions well 0.001). Additionally, potential association between polymorphism TNFRSF1A:rs767455 degree suggested. These suggest increased conditions. should be considered target development new therapeutic options.

Language: Английский

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Poxvirus Immune Evasion

Annual Review of Immunology, Journal Year: 2024, Volume and Issue: 42(1), P. 551 - 584

Published: June 28, 2024

Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview different immunomodulatory strategies. prevent recognition viral DNA that triggers responses inhibit signaling pathways within infected cell. A unique feature poxviruses is production secreted proteins mimic cytokines cytokine receptors, acting as decoy receptors neutralize activity chemokines. The capacity these cellular by inhibiting activation complemented poxviruses' strategies block natural killer cells cytotoxic T cells, often through interfering with antigen presentation pathways. Mechanisms target complement are also encoded poxviruses. Virus-encoded molecules play major role in modulation, their contribution pathogenesis, facilitating virus replication or preventing immunopathology, discussed.

Language: Английский

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TNF deficiency dysregulates inflammatory cytokine production, leading to lung pathology and death during respiratory poxvirus infection

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(27), P. 15935 - 15946

Published: June 22, 2020

Significance Excessive tumor necrosis factor (TNF) production during some respiratory viral infections is associated with lung pathology and death. We show here that deficiency in TNF also causes significant poxvirus infection of mice but has no effect on load. increased interleukin (IL)-6, IL-10, transforming growth beta, interferon gamma overactivation STAT3 signaling. Cytokine blockade, or inactivation, ameliorates TNF-deficient mice. The membrane form alone necessary sufficient for regulating inflammation the prevention pathology. Targeting specific cytokines cytokine signaling pathways to can ameliorate timing duration interventive measures are critical.

Language: Английский

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Viral cGAMP nuclease reveals the essential role of DNA sensing in protection against acute lethal virus infection

Science Advances, Journal Year: 2020, Volume and Issue: 6(38)

Published: Sept. 18, 2020

DNA sensing inhibition by viral cGAMP nuclease impairs anti-viral responses and protective immunity.

Language: Английский

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Targeting tumour necrosis factor to ameliorate viral pneumonia

FEBS Journal, Journal Year: 2021, Volume and Issue: 289(4), P. 883 - 900

Published: Feb. 24, 2021

Pneumonia is a serious complication associated with inflammation of the lungs due to infection viral pathogens. Seasonal and pandemic influenza viruses, variola virus (agent smallpox) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; agent COVID-19) are some leading examples. Viral pneumonia triggered by excessive dysregulated cytokine production, termed 'cytokine storm'. Several cytokines have been implicated but tumour necrosis factor (TNF) plays critical role in driving lung inflammation, pathology death. Despite this, exact TNF aetiology pathogenesis infection-induced complications not well understood. In this review, we discuss pathological immunomodulatory roles contributing immunopathology resolution respectively, mouse models influenza- smallpox (mousepox)-induced pneumonia. We review studies that investigated dampening on outcome orthopoxvirus infections. Most model evaluated efficacy treatment anti-inflammatory drugs, including anti-TNF agents, animal day infection. question merits those as they transferable clinic given individuals generally present at hospital only after onset disease symptoms propose research should be directed determining whether will reduce morbidity mortality. Such strategy more relevant clinically.

Language: Английский

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Macrophages maintain mammary stem cell activity and mammary homeostasis via TNF-α-PI3K-Cdk1/Cyclin B1 axis

npj Regenerative Medicine, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 2, 2023

Adult stem cell niche is a special environment composed of variety stromal cells and signals, which cooperatively regulate tissue development homeostasis. It great interest to study the role immune in niche. Here, we show that mammary resident macrophages epithelium division through TNF-α-Cdk1/Cyclin B1 axis. In vivo, depletion reduces number basal (MaSCs), while increases luminal cells. vitro, establish three-dimensional culture system are co-cultured with macrophages, interestingly, macrophage co-culture promotes formation branched functional organoids. Moreover, TNF-α produced by activates intracellular PI3K/Cdk1/Cyclin signaling cells, thereby maintaining activity MaSCs Together, these findings reveal significance macrophageal axis for MaSC

Language: Английский

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