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Inflammatory Protein Profiles in Plasma of Candidaemia Patients and the Contribution of Host Genetics to Their Variability.

Publication ,  Journal Article
Matzaraki, V; Le, KTT; Jaeger, M; Aguirre-Gamboa, R; Johnson, MD; Sanna, S; Rosati, D; Franke, L; Zhernakova, A; Fu, J; Withoff, S; Jonkers, I ...
Published in: Frontiers in immunology
January 2021

Circulatory inflammatory proteins play a significant role in anti-Candida host immune defence. However, little is known about the genetic variation that contributes to the variability of inflammatory responses in response to C. albicans. To systematically characterize inflammatory responses in Candida infection, we profiled 91 circulatory inflammatory proteins in peripheral blood mononuclear cells (PBMCs) stimulated with C. albicans yeast isolated from 378 individuals of European origin from the 500 Functional Genomics (500FG) cohort of the Human Functional Genomics Project (HFGP) and Lifelines Deep cohort. To identify the genetic factors that determine variation in inflammatory protein responses, we correlated genome-wide single nucleotide polymorphism (SNP) genotypes with protein abundance (protein quantitative trait loci, pQTLs) produced by the Candida-stimulated PBMCs. Furthermore, we investigated whether differences in survival of candidaemia patients can be explained by modulating levels of inflammatory proteins. We identified five genome-wide significant pQTLs that modulate IL-8, MCP-2, MMP-1, and CCL3 in response to C. albicans. In addition, our genetic analysis suggested that GADD45G from rs10114707 locus that reached genome-wide significance could be a potential core gene that regulates a cytokine network upon Candida infection. Last but not least, we observed that a trans-pQTL marked from SNP rs7651677 at chromosome 3 that influences urokinase plasminogen activator (uPA) is strongly associated with patient survival (Psurvival = 3.52 x 10-5, OR 3). Overall, our genetic analysis showed that genetic variation determines the abundance of circulatory proteins in response to Candida infection.

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Published In

Frontiers in immunology

DOI

EISSN

1664-3224

ISSN

1664-3224

Publication Date

January 2021

Volume

12

Start / End Page

662171

Related Subject Headings

  • Young Adult
  • Quantitative Trait Loci
  • Proteomics
  • Proteins
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Leukocytes, Mononuclear
  • Inflammation
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Matzaraki, V., Le, K. T. T., Jaeger, M., Aguirre-Gamboa, R., Johnson, M. D., Sanna, S., … Kumar, V. (2021). Inflammatory Protein Profiles in Plasma of Candidaemia Patients and the Contribution of Host Genetics to Their Variability. Frontiers in Immunology, 12, 662171. https://doi.org/10.3389/fimmu.2021.662171
Matzaraki, Vasiliki, Kieu T. T. Le, Martin Jaeger, Raúl Aguirre-Gamboa, Melissa D. Johnson, Serena Sanna, Diletta Rosati, et al. “Inflammatory Protein Profiles in Plasma of Candidaemia Patients and the Contribution of Host Genetics to Their Variability.Frontiers in Immunology 12 (January 2021): 662171. https://doi.org/10.3389/fimmu.2021.662171.
Matzaraki V, Le KTT, Jaeger M, Aguirre-Gamboa R, Johnson MD, Sanna S, et al. Inflammatory Protein Profiles in Plasma of Candidaemia Patients and the Contribution of Host Genetics to Their Variability. Frontiers in immunology. 2021 Jan;12:662171.
Matzaraki, Vasiliki, et al. “Inflammatory Protein Profiles in Plasma of Candidaemia Patients and the Contribution of Host Genetics to Their Variability.Frontiers in Immunology, vol. 12, Jan. 2021, p. 662171. Epmc, doi:10.3389/fimmu.2021.662171.
Matzaraki V, Le KTT, Jaeger M, Aguirre-Gamboa R, Johnson MD, Sanna S, Rosati D, Franke L, Zhernakova A, Fu J, Withoff S, Jonkers I, Li Y, Joosten LAB, Netea MG, Wijmenga C, Kumar V. Inflammatory Protein Profiles in Plasma of Candidaemia Patients and the Contribution of Host Genetics to Their Variability. Frontiers in immunology. 2021 Jan;12:662171.

Published In

Frontiers in immunology

DOI

EISSN

1664-3224

ISSN

1664-3224

Publication Date

January 2021

Volume

12

Start / End Page

662171

Related Subject Headings

  • Young Adult
  • Quantitative Trait Loci
  • Proteomics
  • Proteins
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Leukocytes, Mononuclear
  • Inflammation
  • Humans