Innate Immune Gene Polymorphisms and COVID-19 Prognosis

Bakaros, Evangelos; Voulgaridi, Ioanna; Paliatsa, Vassiliki; Gatselis, Nikolaos; Germanidis, Georgios; Asvestopoulou, Evangelia; Alexiou, Stamatia; Botsfari, Elli; Lygoura, Vasiliki; Tsachouridou, Olga; Mimtsoudis, Iordanis; Tseroni, Maria; Sarrou, Styliani; Mouchtouri, Varvara A.; Dadouli, Katerina; Kalala, Fani; Metallidis, Simeon; Dalekos, George; Hadjichristodoulou, Christos; Speletas, Matthaios

doi:10.3390/v15091784

Cited by 5 publications

(1 citation statement)

References 44 publications

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“…-Associated with rheumatoid arthritis [103,[105][106][107][108][109], or no association [57,110,111]. -Protective against SARS-CoV-2 [112].…”

Section: Card8 Inhibits Inflammasome Activation and Pro-inflammatory ...mentioning

confidence: 99%

CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity

Karakaya,

Slaufova,

Di Filippo

et al. 2024

Cells

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Inflammasomes comprise a group of protein complexes with fundamental roles in the induction of inflammation. Upon sensing stress factors, their assembly induces the activation and release of the pro-inflammatory cytokines interleukin (IL)-1β and -18 and a lytic type of cell death, termed pyroptosis. Recently, CARD8 has joined the group of inflammasome sensors. The carboxy-terminal part of CARD8, consisting of a function-to-find-domain (FIIND) and a caspase activation and recruitment domain (CARD), resembles that of NLR family pyrin domain containing 1 (NLRP1), which is recognized as the main inflammasome sensor in human keratinocytes. The interaction with dipeptidyl peptidases 8 and 9 (DPP8/9) represents an activation checkpoint for both sensors. CARD8 and NLRP1 are activated by viral protease activity targeting their amino-terminal region. However, CARD8 also has some unique features compared to the established inflammasome sensors. Activation of CARD8 occurs independently of the inflammasome adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), leading mainly to pyroptosis rather than the activation and secretion of pro-inflammatory cytokines. CARD8 was also shown to have anti-inflammatory and anti-apoptotic activity. It interacts with, and inhibits, several proteins involved in inflammation and cell death, such as the inflammasome sensor NLRP3, CARD-containing proteins caspase-1 and -9, nucleotide-binding oligomerization domain containing 2 (NOD2), or nuclear factor kappa B (NF-κB). Single nucleotide polymorphisms (SNPs) of CARD8, some of them occurring at high frequencies, are associated with various inflammatory diseases. The molecular mechanisms underlying the different pro- and anti-inflammatory activities of CARD8 are incompletely understood. Alternative splicing leads to the generation of multiple CARD8 protein isoforms. Although the functional properties of these isoforms are poorly characterized, there is evidence that suggests isoform-specific roles. The characterization of the functions of these isoforms, together with their cell- and disease-specific expression, might be the key to a better understanding of CARD8’s different roles in inflammation and inflammatory diseases.

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“…-Associated with rheumatoid arthritis [103,[105][106][107][108][109], or no association [57,110,111]. -Protective against SARS-CoV-2 [112].…”

Section: Card8 Inhibits Inflammasome Activation and Pro-inflammatory ...mentioning

confidence: 99%

CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity

Karakaya,

Slaufova,

Di Filippo

et al. 2024

Cells

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The Yin and Yang of TLR4 in COVID-19

Mukherjee,

Bayry

2024

Cytokine & Growth Factor Reviews

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Association of TLR2 Arg753Gln gene polymorphism with its expression level in nonagenarians with frailty

Lukyanova,

Artemieva,

Nasaeva

et al. 2024

Med. immunol.

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TLR2 is an exceptional pattern-recognizing receptor because of its ability to heterodimerise with different types of TLRs, which allows it to recognize a wide range of molecular structures on the surface of pathogens. Polymorphisms in genes involved in the TLRs signaling cascade may be a factor in host susceptibility to the development of inflammation, affecting the outcome of a number of infectious diseases and immune diseases. The variant Arg753Gln (rs5743708) in the TLR2 gene is the most characterized missense mutation of the coding region in the TIR domain, which involves the substitution of arginine for glutamine at position 753 of the protein sequence. This functionally significant substitution leads to altered signaling and is associated with inflammatory responses. In this study, we investigated the association of the Arg753Gln (rs5743708) polymorphism of the TLR2 gene with the level of its expression in nonagenarians. The study included 82 nonagenarians. Frailty was detected in 41 subjects using a short physical performance battery, with registration in the test ≤ 7 points. It was shown that carriage of the Gln allele is statistically significantly associated with an increased risk of developing frailty; patients with the Arg/Gln genotype have a 12.8-fold higher chance of developing this geriatric syndrome. The Arg allele and the Arg/Arg genotype were found to be protective factors in the development of frailty in nonagenarians. Analysis of TLR2 gene expression in nonagenarians revealed a 2.79-fold increase in TLR2 expression relative to donors. Evaluation of TLR2 gene expression level in groups of nonagenarians with the presence and absence of frailty showed a 1.4-fold increase in TLR2 gene expression in nonagenarians with this geriatric syndrome. In patients with the Arg/Gln genotype, TLR2 gene expression was 1.3 times higher than in the group with the Arg/Arg genotype and 1.6 times higher than in the group with the Gln/Gln genotype. The increased frequency of occurrence of the Arg/Gln genotype of the Arg753Gln polymorphism of the TLR2 gene in nonagenarians with frailty may be due to increased gene expression of this receptor. It is necessary to conduct further functional and molecular genetic studies.

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Innate Immune Gene Polymorphisms and COVID-19 Prognosis

Cited by 5 publications

References 44 publications

CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity

CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity

The Yin and Yang of TLR4 in COVID-19

Association of TLR2 Arg753Gln gene polymorphism with its expression level in nonagenarians with frailty

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