Histone deacetylase-2 controls IL-1β production through the regulation of NLRP3 expression and activation in tuberculosis infection

Moreira, Jôsimar Dornelas; Iakhiaev, Alexei; Vankayalapati, Ramakrishna; Jung, Barbara; Samten, Buka

doi:10.1016/j.isci.2022.104799

Cited by 9 publications

(3 citation statements)

References 70 publications

(101 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results showed that the down-regulation of microRNA 145 expression detected in atherosclerotic plaques could induce NLRP3 inflammasome activation, and the decrease in microRNA 145 expression was associated with the enrichment of DNMT1 and the hypermethylation status of its promoter [ 118 ]. In addition, other studies have shown that HDAC6 and HDAC2 are also involved in the activation of NLRP3 inflammasomes in inflammatory diseases such as tuberculosis infection [ 119 , 120 ]. Glycolic acid stimulation of human immortalized keratinocytes induces DNMT3B recruitment in NLRC4 inflammasome and inhibits the transcriptional expression of NLRC4 and ASC, which may lead to the blockage of NLRC4 inflammasome assembly [ 121 ].…”

Section: Role Of Chromatin Modifiers In Human Diseasesmentioning

confidence: 99%

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Nie,

Song,

Huang

et al. 2024

Mol Biomed

View full text Add to dashboard Cite

The field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by regulating chromatin accessibility and the ability of transcription factors to acquire DNA. This is achieved by recruiting associated proteins and RNA polymerases. They modify the physical contact between cis-regulatory factor elements, transcription factors, and chromatin DNA to influence transcriptional regulatory processes. Then, abnormal chromatin perturbations can impair the homeostasis of organs, tissues, and cells, leading to diseases. The review offers a comprehensive elucidation on the function and regulatory mechanism of chromatin modifiers, thereby highlighting their indispensability in the development of diseases. Furthermore, this underscores the potential of chromatin modifiers as biomarkers, which may enable early disease diagnosis. With the aid of this paper, a deeper understanding of the role of chromatin modifiers in the pathogenesis of diseases can be gained, which could help in devising effective diagnostic and therapeutic interventions.

show abstract

Section: Role Of Chromatin Modifiers In Human Diseasesmentioning

confidence: 99%

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Nie,

Song,

Huang

et al. 2024

Mol Biomed

View full text Add to dashboard Cite

show abstract

“…Three additional mice were included in the Madison chamber at the time of infection and were euthanized 24 hours after infection. The lungs were collected, macerated and plated on 7H10 agar to confirm the initial bacterial implantation (33).…”

Section: Animal Experiments Designmentioning

confidence: 99%

A novel humanized mouse model for HIV and tuberculosis co-infection studies

Bohórquez,

Adduri,

Ansari

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

BackgroundTuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. HIV infection decreases CD4+ T cell levels markedly increasing Mtb co-infections. An appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans during co-infection would facilitate basic and translational research in HIV/Mtb infections. Herein, we describe a novel humanized mouse model.MethodsThe irradiated NSG-SGM3 mice were transplanted with human CD34+ hematopoietic stem cells, and the humanization was monitored by staining various immune cell markers for flow cytometry. They were challenged with HIV and/or Mtb, and the CD4+ T cell depletion and HIV viral load were monitored over time. Before necropsy, the live mice were subjected to pulmonary function test and CT scan, and after sacrifice, the lung and spleen homogenates were used to determine Mtb load (CFU) and cytokine/chemokine levels by multiplex assay, and lung sections were analyzed for histopathology. The mouse sera were subjected to metabolomics analysis.ResultsOur humanized NSG-SGM3 mice were able to engraft human CD34+ stem cells, which then differentiated into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced granulomatous lesions in the lungs. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections.ConclusionThe humanized NSG-SGM3 mice are able to recapitulate the pathogenic effects of HIV and Mtb infections and co-infection at the pathological, immunological and metabolism levels and are therefore a reproducible small animal model for studying HIV/Mtb co-infection.

show abstract

“…The regulation of inflammasomes occurs at the transcription and post-translation levels [35]. For example, epigenetic factors, such as DNA methylation and histone acetylation, control the NLRP3 transcriptional in mycobacterial infections [36,37]. MicroRNA is another known regulator of inflammasomes.…”

Section: Negative Regulation Of Inflammasomesmentioning

confidence: 99%

Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis

Sharma,

Ismail

2023

Cells

View full text Add to dashboard Cite

Activating inflammatory caspases and releasing pro-inflammatory mediators are two essential functions of inflammasomes which are triggered in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). The canonical inflammasome pathway involves the activation of inflammasome and its downstream pathway via the adaptor ASC protein, which causes caspase 1 activation and, eventually, the cleavage of pro-IL-1b and pro-IL-18. The non-canonical inflammasome pathway is induced upon detecting cytosolic lipopolysaccharide (LPS) by NLRP3 inflammasome in Gram-negative bacteria. The activation of NLRP3 triggers the cleavage of murine caspase 11 (human caspase 4 or caspase 5), which results in the formation of pores (via gasdermin) to cause pyroptosis. Ehrlichia is an obligately intracellular bacterium which is responsible for causing human monocytic ehrlichiosis (HME), a potentially lethal disease similar to toxic shock syndrome and septic shock syndrome. Several studies have indicated that canonical and non-canonical inflammasome activation is a crucial pathogenic mechanism that induces dysregulated inflammation and host cellular death in the pathophysiology of HME. Mechanistically, the activation of canonical and non-canonical inflammasome pathways affected by virulent Ehrlichia infection is due to a block in autophagy. This review aims to explore the significance of non-canonical inflammasomes in ehrlichiosis, and how the pathways involving caspases (with the exception of caspase 1) contribute to the pathophysiology of severe and fatal ehrlichiosis. Improving our understanding of the non-canonical inflammatory pathway that cause cell death and inflammation in ehrlichiosis will help the advancement of innovative therapeutic, preventative, and diagnostic approaches to the treatment of ehrlichiosis.

show abstract

Histone deacetylase-2 controls IL-1β production through the regulation of NLRP3 expression and activation in tuberculosis infection

Cited by 9 publications

References 70 publications

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

A novel humanized mouse model for HIV and tuberculosis co-infection studies

Non-Canonical Inflammasome Pathway: The Role of Cell Death and Inflammation in Ehrlichiosis

Contact Info

Product

Resources

About