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CD14 expression in the first 24h of sepsis: effect of -260C>T CD14 SNP
Bibiana Butkus de Aguiar1, Ingrid Girardi, Diego D'Avila Paskulin
1Faculdade de Biociências and Hospital São Lucas (HSL), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil.
Abstract:
Sepsis is defined as systemic inflammation caused by infection. The membrane bound CD14 (mCD14) or the soluble form (sCD14) play a crucial role facing Gram-negative and Gram-positive sepsis since they are pattern recognition receptors of the innate immune response enabling cells to produce inflammatory cytokines against bacterial infections. A -260C>T single nucleotide polymorphism (SNP) was detected in the promoter modulating the CD14 gene expression. We hypothesized that the CD14 expression depends of the genetic inheritance of -260C>T CD14 SNP and it is modulated by sepsis condition. We investigated human CD14 expression on early sepsis diagnosis (in vivo) and after LPS stimulation (in vitro), and determined the -260C>T CD14 SNP. We found that TT homozygotes showed higher mCD14 density (p = 0.0207), but not different sCD14 levels when compared to the CT+CC genotypes. Monocyte mCD14 density and sCD14 serum levels in our sample of early 14 septic patients were significantly higher than normal 30 controls (p<0.0001). Our results suggest that the -260TT CD14 genotype is associated with higher monocyte mCD14, but not sCD14 expression, and that in the first 24 h after sepsis diagnosis, both monocyte mCD14 density and sCD14 levels are elevated, similarly to what is observed in vitro upon challenge with LPS.
Insights
The CD14 gene's -260TT genotype is linked to higher monocyte membrane-bound CD14 (mCD14) levels. Sepsis patients show elevated mCD14 and soluble CD14 (sCD14) in early diagnosis.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Sepsis involves systemic inflammation due to infection.
- CD14 (membrane-bound mCD14 and soluble sCD14) acts as a pattern recognition receptor in innate immunity, crucial for responding to Gram-negative and Gram-positive bacteria.
- A single nucleotide polymorphism (-260C>T) in the CD14 gene promoter influences its expression.
Purpose of the Study:
- To investigate if the -260C>T CD14 single nucleotide polymorphism (SNP) affects CD14 gene expression.
- To determine how sepsis influences CD14 expression in vivo and in vitro.
- To explore the association between CD14 genotypes and CD14 expression levels in sepsis.
Main Methods:
- Genotyping for the -260C>T CD14 SNP.
- Quantification of monocyte membrane-bound CD14 (mCD14) density.
- Measurement of soluble CD14 (sCD14) serum levels.
- In vivo analysis in early sepsis patients and healthy controls.
- In vitro analysis using lipopolysaccharide (LPS) stimulation.
Main Results:
- Individuals with the TT genotype exhibited higher monocyte mCD14 density compared to CT+CC genotypes (p = 0.0207).
- No significant difference in sCD14 levels was observed between genotypes.
- Sepsis patients displayed significantly higher monocyte mCD14 density and sCD14 serum levels than controls (p<0.0001).
- Elevated mCD14 and sCD14 levels were observed within 24 hours of sepsis diagnosis, mirroring in vitro LPS challenge results.
Conclusions:
- The -260TT CD14 genotype is associated with increased monocyte mCD14 expression, but not sCD14 levels.
- Early sepsis diagnosis is characterized by elevated levels of both monocyte mCD14 and sCD14.
- CD14 genotype and sepsis status interact to modulate CD14 expression, impacting innate immune response.