Functional polymorphisms in the gene encoding macrophage migration inhibitory factor are associated with Gram-negative bacteremia in older adults

J Infect Dis. 2014 Mar 1;209(5):764-8. doi: 10.1093/infdis/jit571. Epub 2013 Oct 24.

Abstract

Macrophage migration inhibitory factor (MIF) is an immune mediator encoded in a functionally polymorphic locus. We found the genotype conferring low expression of MIF to be enriched in a cohort of 180 patients with gram-negative bacteremia, compared with 229 healthy controls (odds ratio [OR], 2.4; P = .04), an association that was more pronounced in older adults (OR, 4.6; P = .01). Among older subjects, those with low expression of MIF demonstrated 20% reduced MIF production from lipopolysaccharide-stimulated peripheral blood monocytes and 30% lower monocyte surface Toll-like receptor 4, compared with those with high expression. Our work suggests that older adults with low expression of MIF may be predisposed to hyporesponsiveness to lipopolysaccharide and gram-negative bacterial infection.

Keywords: MIF; gram-negative infection; immune response; macrophage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteremia / genetics*
  • Bacteremia / metabolism
  • Female
  • Genotype
  • Gram-Negative Bacteria / metabolism
  • Gram-Negative Bacterial Infections / genetics*
  • Gram-Negative Bacterial Infections / metabolism
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Intramolecular Oxidoreductases / genetics*
  • Intramolecular Oxidoreductases / metabolism
  • Macrophage Migration-Inhibitory Factors / genetics*
  • Macrophage Migration-Inhibitory Factors / metabolism
  • Macrophages / metabolism*
  • Macrophages / microbiology
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • Macrophage Migration-Inhibitory Factors
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Intramolecular Oxidoreductases
  • MIF protein, human