Deciphering the TLR transcriptome and downstream signaling pathway in cerebrospinal fluid in pediatric meningitis

Salaria, M; Singhi, Sunit; Singhi, Pratibha; Sharma, Madhulika; Mangat, Navdeep; Bhatia, Tanvi; Wickström, Ronny; Aggarwal, Ritu

doi:10.1007/s00011-022-01562-6

Cited by 2 publications

(3 citation statements)

References 28 publications

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“…It can exhibit inhibitive effect on different viral infections including Zika, Ebola, and SARS‐CoV‐2 34 . Toll‐like receptor 3 (TLR3) is a member of the TLR family, which regulates the transcriptional induction of type I interferons (IFNs) and proinflammatory cytokines to build an antiviral host response 35 . By testing the gene expression in peripheral blood, researchers have found that TLR3 was associated with clinical severity in COVID‐19 patients 36 .…”

Section: Discussionmentioning

confidence: 99%

“… 34 Toll‐like receptor 3 (TLR3) is a member of the TLR family, which regulates the transcriptional induction of type I interferons (IFNs) and proinflammatory cytokines to build an antiviral host response. 35 By testing the gene expression in peripheral blood, researchers have found that TLR3 was associated with clinical severity in COVID‐19 patients. 36 In diabetic skin wounds, activation of TLR3 can induce tissue destruction by triggering the production of proinflammatory cytokines and reactive oxygen species.…”

Section: Discussionmentioning

confidence: 99%

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Mining the potential therapeutic targets for COVID‐19 infection in patients with severe burn injuries via bioinformatics analysis

Cai

Deng

Shi

et al. 2023

International Wound Journal

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The Coronavirus Disease‐19 (COVID‐19) pandemic is posing a serious challenge to human health. Burn victims are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection leading to delayed recovery and even profound debilitation. Nevertheless, the molecular mechanisms underlying COVID‐19 and severe burn are yet to be elucidated. In our work, the differentially expressed genes (DEGs) were identified from GSE157852 and GSE19743, and the common DEGs between COVID‐19 and severe burn were extracted. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interactions (PPI), gene coexpression network, and multifactor regulatory network analysis of hub genes were carried out. A total of 44 common DEGs were found between COVID‐19 and severe burn. Functional analyses indicated that the pathways of immune regulation and cytokine response participated collectively in the development of severe burn and progression of COVID‐19. Ten significant hub genes were identified, including MERTK, SIRPA, TLR3, ITGB1, DPP4, PTPRC, LY75, IFIT1, IL4R, and CD2. In addition, the gene coexpression network and regulatory network were constructed containing 42 microRNAs (miRNAs) and 2 transcription factors (TFs). Our study showed the shared pathogenic link between COVID‐19 and severe burn. The identified common genes and pivotal pathways pave a new road for future mechanistic researches in severe burn injuries complicated with COVID‐19.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mining the potential therapeutic targets for COVID‐19 infection in patients with severe burn injuries via bioinformatics analysis

Cai

Deng

Shi

et al. 2023

International Wound Journal

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“…Data from animal models and children with PM suggest excessive inflammatory responses determine disease severity, 8,11,23 however the mechanisms of tissue damage from the host-pathogen interaction in PM remain poorly understood, and few tractable therapeutic targets have been identified to date 6,[23][24][25][26] .Transcriptional profiling in infectious diseases offers an opportunity to describe the immunomodulatory processes associated invasive infection in greater depth [27][28][29] . Meningitisspecific transcriptomic data in children with tuberculous meningitis (TBM) have shown compartmentalisation of neurological damage within the CNS, compartment compared to inflammasome activation in serum, whereas in neonates with bacterial meningitis (BM) caused by a range of pathogens, transcriptome data suggest activation of TLR-signalling pathways in CSF and an evolution of the cellular response over time 30,31 . Whilst informative, these reports are not directly relevant to adult PM, particularly towards amelioration of intractably poor clinical outcomes.…”

mentioning

confidence: 99%

The CSF transcriptome in pneumococcal meningitis reveals compartmentalised host inflammatory responses associated with mortality

Guerra-Assunção,

Chakravarty,

Pollara

et al. 2024

Preprint

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BackgroundPneumococcal meningitis (PM) has persistently poor clinical outcomes, especially in sub- Saharan Africa. To better characterise the inflammatory response and identify factors associated with mortality we compared paired peripheral blood and cerebrospinal fluid (CSF) transcriptomes before the initiation of antibiotics in Malawian adults with proven PM.ResultsBlood transcriptional profiles were obtained in 28 patients with PM, with simultaneous paired with CSF profiles available for 13 patients. 15/28 (52%) patients died. Comparison of the transcriptome between CSF and blood compartments showed upregulation of 2293 differentially expressed genes in CSF and 909 in blood; enriched pathways in CSF included inflammasome activity and neutrophil migration/activation in the CSF, contrasting with enrichment for pathways including platelet and endothelial activation, cell cycle, cytokine release and oxidative stress in the blood transcriptome. Comparison of CSF profiles between survivors and non-survivors revealed 1829 differentially expressed genes, non- survivor CSF was enriched for multiple innate inflammatory pathways, including IL-17A and Type 1 interferons and proteolysis. In contrast, minimal transcriptomic differences between outcome groups were detected in blood.ConclusionInflammation in PM is characterised by compartmentalised responses in blood and CSF. Poorer outcomes are associated with an dysregulated innate immune host response toS. pneumoniaein the CSF compartment.

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Deciphering the TLR transcriptome and downstream signaling pathway in cerebrospinal fluid in pediatric meningitis

Cited by 2 publications

References 28 publications

Mining the potential therapeutic targets for COVID‐19 infection in patients with severe burn injuries via bioinformatics analysis

Mining the potential therapeutic targets for COVID‐19 infection in patients with severe burn injuries via bioinformatics analysis

The CSF transcriptome in pneumococcal meningitis reveals compartmentalised host inflammatory responses associated with mortality

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