Inflammasome activation by viral infection: mechanisms of activation and regulation

Shi, Weisong; Jin, Mengyun; Chen, Honglin; Wu, Zongxue; Yuan, L.; Liang, Sai; Wang, X; Memon, Fareed Uddin; Eldemery, Fatma; Si, Hongbin; Ou, Changbo

doi:10.3389/fmicb.2023.1247377

Cited by 9 publications

(3 citation statements)

References 144 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additional hypermethylation was observed in genes associated with the inflammasome pathway in IAP children, including PCSK6 [ 25 ], NLRP1 [ 26 ], FLT4 and IL18RAP [ 27 ] 28 , suggesting deficits in anti-viral defenses. Furthermore, hypermethylation was also observed in immune response genes including MAP3K6 , KSR1 [ 29 ] and PARP9 [ 30 ], implicated in the IFN-γ response.…”

Section: Resultsmentioning

confidence: 99%

Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways

Martino,

Schultz,

Kaur

et al. 2024

Clin Epigenet

View full text Add to dashboard Cite

Background Infants with frequent viral and bacterial respiratory infections exhibit compromised immunity to routine immunizations. They are also more likely to develop chronic respiratory diseases in later childhood. This study investigated the feasibility of epigenetic profiling to reveal endotype-specific molecular pathways with potential for early identification and immuno-modulation. Peripheral blood mononuclear cells from respiratory infection allergy/asthma-prone (IAP) infants and non-infection allergy/asthma prone (NIAP) were retrospectively selected for genome-wide DNA methylation and single nucleotide polymorphism analysis. The IAP infants were enriched for the low vaccine responsiveness (LVR) phenotype (Fisher's exact p-value = 0.02). Results An endotype signature of 813 differentially methylated regions (DMRs) comprising 238 lead CpG associations (FDR < 0.05) emerged, implicating pathways related to asthma, mucin production, antigen presentation and inflammasome activation. Allelic variation explained only a minor portion of this signature. Stimulation of mononuclear cells with monophosphoryl lipid A (MPL), a TLR agonist, partially reversed this signature at a subset of CpGs, suggesting the potential for epigenetic remodeling. Conclusions This proof-of-concept study establishes a foundation for precision endotyping of IAP children and highlights the potential for immune modulation strategies using adjuvants for future investigation.

show abstract

Section: Resultsmentioning

confidence: 99%

Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways

Martino,

Schultz,

Kaur

et al. 2024

Clin Epigenet

View full text Add to dashboard Cite

show abstract

“…A large number of viruses can overactivate the NLRP3 inflammasome [63]. For exemple, according to World Health Organization (WHO) the seasonal influenza causes 3-5 million cases of severe illnesses and between 290,000 and 650,000 deaths per year globally, with 36% of these deaths taking place in low-and middle income countries (Influenza (Seasonal).…”

Section: Future Directionsmentioning

confidence: 99%

Colchicine—The Divine Medicine against COVID-19

Mitev

2024

Preprint

View full text Add to dashboard Cite

Colchicine has a number of effects that suggest it may be useful in the treatment of COVID-19. Myeloid cells are a major source of dysregulated inflammation in COVID-19. The hyperactivation of the NLRP3 inflammasome and the subsequent cytokine storm take place precisely inside them and can lead to multiorgan damage and death. NLRP3 inflammasome inhibition has been assessed at micromolar colchicine concentrations which cannot be achieved in serum. However, colchicine has remarkable ability to accumulate intensively in leukocytes, where the cytokine storm is generated. Over 50 observational studies and randomized clinical trials, small randomized non-controlled trials and retrospective cohort studies were initiated to test its healing effect in vivo, leading to conflicting, rather disappointing results. WHO gives ”Strong recommendation against” the use of colchicine for COVID-19 treatment. This is because low doses of colchicine are always used, where the concentrations required to inhibit the NLRP3 inflammasome in leukocytes cannot be reached. Considering this, from March 2020 we started the administration of higher doses of colchicine. Our assumption was that safe increase in colchicine doses to reach micromolar concentrations in leukocytes will result in NLRP3 inflammasome/cytokine storm inhibition. We demonstrated that in 785 inpatients treated with increasing doses of colchicine, mortality fell between 2 and 7 times. Our data, including also a large number of COVID-19 outpatients, showed that nearly 100% of the patients treated with this therapeutic regimen escaped hospitalization. In addition, post-covid symptoms in those treated with colchicine were significantly less. As a large number of viruses can overactivate the NLRP3 inflammasome (like seasonal influenza), we are convinced that higher colchicine doses would be useful in these cases as well.

show abstract

“…As a defensive reaction from the innate immune system during various diseases and infections or stress conditions, a polymeric structure known as in ammasome composed of sensor proteins, junction molecules, and effectors is assembled [11]. The in ammatory response is triggered by the in ammasome, which releases various in ammatory factors such as Interleukin IL-1β (IL-1β), Interleukin IL-18 (IL-18), and Interleukin IL-37 [12].…”

Section: Introductionmentioning

confidence: 99%

Secukinumab’ Cardioprotective Effect in Doxorubicin-induced cardiomyopathy: Targeting the NF-κB/NLRP3 Pathway in Rats

Hassen,

Mousa,

Radwan

et al. 2024

Preprint

View full text Add to dashboard Cite

Doxorubicin (DOX) is a medication employed in the treatment of cancer as a chemotherapeutic agent. However, it induces cardiotoxicity via activating inflammatory pathways. Cytokines dysregulation is a key factor that can lead to activation of inflammatory mechanisms. Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that triggers pathogenic immune responses. The objective of this study was to investigate the defensive power of secukinumab (SEC), a fully human monoclonal IgG1/κ antibody targeting IL-17A, designed to combat DOX-induced cardiotoxicity (DIC). Male Wistar rats were treated with DOX and co-treated with SEC for two weeks. The results showed that DOX caused heart tissue injury, increased cardiotoxicity markers significantly (P < 0.0001), oxidative stress and inflammation. Additionally, DOX activated the nuclear factor kappa beta (NF-κB) pathway and Pyrin domain containing 3 (NLRP3) inflammasome, potentially contributing to DIC. The co-treatment with SEC successfully reversed all DOX-related abnormalities by restoring cardiac functions to normal levels, decreasing levels of inflammatory cytokines, including IL-17A and Interleukin-1β (IL-1β), and improving oxidative stress by lowering malondialdhyde (MDA) levels and increasing reduced glutathione (GSH) levels. Furthermore, it also decreased the upregulation of the NF-κB/NLRP3 axis induced by doxorubicin. This study highlights the protective properties of SEC against DIC by modulating the NF-κB/NLRP3/caspase1/IL-1β axis.

show abstract

Inflammasome activation by viral infection: mechanisms of activation and regulation

Cited by 9 publications

References 144 publications

Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways

Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways

Colchicine—The Divine Medicine against COVID-19

Secukinumab’ Cardioprotective Effect in Doxorubicin-induced cardiomyopathy: Targeting the NF-κB/NLRP3 Pathway in Rats

Contact Info

Product

Resources

About