Serum matrix metalloproteinase-9 (MMP-9) as a biomarker in paediatric and adult tick-borne encephalitis patients

Fořtová, Andrea; Hönig, Václav; Salát, Jiřı́; Palus, Martin; Pýchová, Martina; Krbková, Lenka; Barkhash, Andrey V.; Kriha, Michal F.; Chrdle, Aleš; Lipoldová, Marie; Růžek, Daniel

doi:10.1016/j.virusres.2022.199020

Cited by 9 publications

(10 citation statements)

References 37 publications

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“…Endogenous proteases, including gelatinases such as MMPs, play significant roles in the pathogenesis of flavivirus encephalitis. MMP-9, for example, is upregulated during flavivirus encephalitis and contributes to BBB breakdown by degrading TJ proteins and extracellular matrix components like collagen (46)(47)(48). This proteolytic activity facilitates the infiltration of immune cells into the CNS, exacerbating neuroinflammation and tissue damage (49,50).…”

Section: Discussionmentioning

confidence: 99%

Astrocytic RIPK3 exerts protective anti-inflammatory activity during viral encephalitis via induction of serpin protease inhibitors

Lindman,

Estevez,

Marmut

et al. 2024

Preprint

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Flaviviruses pose a significant threat to public health due to their ability to infect the central nervous system (CNS) and cause severe neurologic disease. Astrocytes play a crucial role in the pathogenesis of flavivirus encephalitis through their maintenance of blood-brain barrier (BBB) integrity and their modulation of immune cell recruitment and activation within the CNS. We have previously shown that receptor interacting protein kinase-3 (RIPK3) is a central coordinator of neuroinflammation during CNS viral infection, a function that occurs independently of its canonical function in inducing necroptotic cell death. To date, however, roles for necroptosis-independent RIPK3 signaling in astrocytes are poorly understood. Here, we use mouse genetic tools to induce astrocyte-specific deletion, overexpression, and chemogenetic activation of RIPK3 to demonstrate an unexpected anti-inflammatory function for astrocytic RIPK3. RIPK3 activation in astrocytes was required for host survival in multiple models of flavivirus encephalitis, where it restricted neuropathogenesis by limiting immune cell recruitment to the CNS. Transcriptomic analysis revealed that, despite inducing a traditional pro-inflammatory transcriptional program, astrocytic RIPK3 paradoxically promoted neuroprotection through the upregulation of serpins, endogenous protease inhibitors with broad immunomodulatory activity. Notably, intracerebroventricular administration of SerpinA3N in infected mice preserved BBB integrity, reduced leukocyte infiltration, and improved survival outcomes in mice lacking astrocytic RIPK3. These findings highlight a previously unappreciated role for astrocytic RIPK3 in suppressing pathologic neuroinflammation and suggests new therapeutic targets for the treatment of flavivirus encephalitis.

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Section: Discussionmentioning

confidence: 99%

Astrocytic RIPK3 exerts protective anti-inflammatory activity during viral encephalitis via induction of serpin protease inhibitors

Lindman,

Estevez,

Marmut

et al. 2024

Preprint

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“…Although it did correlate with estimated exposure levels, it was not significantly associated with urinary As levels. Serum MMP-9 is also a potential biomarker for other conditions including tick-borne encephalitis [27], brain tumors [28], and alcohol intoxication in adolescents [29]. The specificity of these biomarkers needs to be considered.…”

Section: Biomarkers Of Effect 41 Arsenicmentioning

confidence: 99%

E-Waste and Metal Contamination in the Environment: Health Effects

Dockrell¹,

Purchase²,

Price³

2023

Trace Metals in the Environment

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It is predicted that electronic waste (e-waste) derived principally from discarded electronic equipment will reach 74 million metric tonnes by 2030. In addition, urbanisation and industrialisation have contributed to metal contamination in the environment. E-waste is often deposed of in low-income countries adversely affecting the health of the working population. The main sources of e-contamination are soil, dust, and food matrices. Drinking water can also be contaminated with heavy metals such as arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) causing a major health concern. Exposure to pollutants present in waste is a common cause of kidney and other diseases primarily amongst children in developing countries. Sensitive monitoring procedures are needed to improve the rate of detection and monitoring of the possible adverse effects on the population exposed to significant quantities of e-waste.

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“…Also, a functional Toll-like receptor 3 gene ( TLR3 ) and nonfunctional CCR5Δ32 mutation were found to be risk factors for TBE (Kindberg et al 2008 ; Mickienė et al 2014 ). However, our recent work shows that genetic determinants may differ greatly between different populations, as the role of the MMP9 SNP in TBE predisposition clearly demonstrated in Russian residents was not observed in Czech TBE patients (Fortova et al 2023 ). This highlights the importance of studying genetic markers of TBE predisposition in different populations living in TBE endemic areas.…”

Section: Introductionmentioning

confidence: 97%

Genetic polymorphisms in innate immunity genes influence predisposition to tick-borne encephalitis

Fortova,

Barkhash,

Pychova

et al. 2023

J. Neurovirol.

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Tick-borne encephalitis (TBE) is a neuroviral disease that ranges in severity from a mild febrile illness to a severe and life-threatening meningoencephalitis or encephalomyelitis. There is increasing evidence that susceptibility to tick-borne encephalitis virus (TBEV)-induced disease and its severity are largely influenced by host genetic factors, in addition to other virus- and host-related factors. In this study, we investigated the contribution of selected single nucleotide polymorphisms (SNPs) in innate immunity genes to predisposition to TBE in humans. More specifically, we investigated a possible association between SNPs rs304478 and rs303212 in the gene Interferon Induced Protein With Tetratricopeptide Repeats 1 (IFIT1), rs7070001 and rs4934470 in the gene Interferon Induced Protein With Tetratricopeptide Repeats 2 (IFIT2), and RIG-I (Retinoic acid-inducible gene I) encoding gene DDX58 rs311795343, rs10813831, rs17217280 and rs3739674 SNPs with predisposition to TBE in population of the Czech Republic, where TBEV is highly endemic. Genotypic and allelic frequencies for these SNPs were analyzed in 247 nonimmunized TBE patients and compared with 204 control subjects. The analysis showed an association of IFIT1 rs304478 SNP and DDX58 rs3739674 and rs17217280 SNPs with predisposition to TBE in the Czech population indicating novel risk factors for clinical TBE but not for disease severity. These results also highlight the role of innate immunity genes in TBE pathogenesis.

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Serum matrix metalloproteinase-9 (MMP-9) as a biomarker in paediatric and adult tick-borne encephalitis patients

Cited by 9 publications

References 37 publications

Astrocytic RIPK3 exerts protective anti-inflammatory activity during viral encephalitis via induction of serpin protease inhibitors

Astrocytic RIPK3 exerts protective anti-inflammatory activity during viral encephalitis via induction of serpin protease inhibitors

E-Waste and Metal Contamination in the Environment: Health Effects

Genetic polymorphisms in innate immunity genes influence predisposition to tick-borne encephalitis

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