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Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi.

ABSTRACT: Little is known about the inter-individual variation of cytokine responses to different pathogens in healthy individuals. To systematically describe cytokine responses elicited by distinct pathogens and to determine the effect of genetic variation on cytokine production, we profiled cytokines produced by peripheral blood mononuclear cells from 197 individuals of European origin from the 200 Functional Genomics (200FG) cohort in the Human Functional Genomics Project (http://www.humanfunctionalgenomics.org), obtained over three different years. We compared bacteria- and fungi-induced cytokine profiles and found that most cytokine responses were organized around a physiological response to specific pathogens, rather than around a particular immune pathway or cytokine. We then correlated genome-wide single-nucleotide polymorphism (SNP) genotypes with cytokine abundance and identified six cytokine quantitative trait loci (QTLs). Among them, a cytokine QTL at the NAA35-GOLM1 locus markedly modulated interleukin (IL)-6 production in response to multiple pathogens and was associated with susceptibility to candidemia. Furthermore, the cytokine QTLs that we identified were enriched among SNPs previously associated with infectious diseases and heart diseases. These data reveal and begin to explain the variability in cytokine production by human immune cells in response to pathogens.

SUBMITTER: Li Y

PROVIDER: S-EPMC5084084 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi.

Li Yang Y Oosting Marije M Deelen Patrick P Ricaño-Ponce Isis I Smeekens Sanne S Jaeger Martin M Matzaraki Vasiliki V Swertz Morris A MA Xavier Ramnik J RJ Franke Lude L Wijmenga Cisca C Joosten Leo A B LA Kumar Vinod V Netea Mihai G MG

Nature medicine 20160704 8

Little is known about the inter-individual variation of cytokine responses to different pathogens in healthy individuals. To systematically describe cytokine responses elicited by distinct pathogens and to determine the effect of genetic variation on cytokine production, we profiled cytokines produced by peripheral blood mononuclear cells from 197 individuals of European origin from the 200 Functional Genomics (200FG) cohort in the Human Functional Genomics Project (http://www.humanfunctionalgen ...[more]

PMID: 27376574

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Project description:BACKGROUND:Relatively high serum carotenoid levels are associated with reduced risks of chronic diseases, but inter-individual variability in serum carotenoid concentrations is modestly explained by diet. The bacterial community in the colon could contribute to the bioaccessibility of carotenoids by completing digestion of plant cells walls and by modulating intestinal permeability. OBJECTIVE:To evaluate whether colonic bacterial composition is associated with serum and colon carotenoid concentrations. DESIGN:The study was a randomized dietary intervention trial in healthy individuals who were at increased risk of colon cancer. Colon mucosal biopsy samples were obtained before and after 6 months of intervention without prior preparation of the bowels. PARTICIPANTS/SETTING:Participants were recruited from Ann Arbor, MI, and nearby areas from July 2007 to November 2010. Biopsy data were available from 88 participants at baseline and 82 participants after 6 months. METHODS:Study participants were randomized to counseling for either a Mediterranean diet or a Healthy Eating diet for 6 months. RESULTS:At baseline, bacterial communities in biopsy samples from study participants in the highest vs the lowest tertile of total serum carotenoid levels differed by several parameters. Linear discriminant analysis effect size identified 11 operational taxonomic units that were significantly associated with higher serum carotenoid levels. In linear regression analyses, three of these accounted for an additional 12% of the variance in serum total carotenoid concentrations after including body mass index, smoking, and dietary intakes in the model. These factors together explained 36% of the inter-individual variance in serum total carotenoid concentrations. The bacterial community in the colonic mucosa, however, was resistant to change after dietary intervention with either a Mediterranean diet or Healthy Eating diet, each of which doubled fruit and vegetable intakes. CONCLUSIONS:The colonic mucosal bacterial community was associated with serum carotenoid concentrations at baseline but was not appreciably changed by dietary intervention.

Dataset Information

Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi.

Publications

Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi.

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