Host Polymorphisms in TLR9 and IL10 Are Associated With the Outcomes of Experimental Haemophilus ducreyi Infection in Human Volunteers

J Infect Dis. 2016 Aug 1;214(3):489-95. doi: 10.1093/infdis/jiw164. Epub 2016 Apr 27.

Abstract

Background: In humans inoculated with Haemophilus ducreyi, there are host effects on the possible clinical outcomes-pustule formation versus spontaneous resolution of infection. However, the immunogenetic factors that influence these outcomes are unknown. Here we examined the role of 14 single-nucleotide polymorphisms (SNPs) in 7 selected pathogen-recognition pathways and cytokine genes on the gradated outcomes of experimental infection.

Methods: DNAs from 105 volunteers infected with H. ducreyi at 3 sites were genotyped for SNPs, using real-time polymerase chain reaction. The participants were classified into 2 cohorts, by race, and into 4 groups, based on whether they formed 0, 1, 2, or 3 pustules. χ(2) tests for trend and logistic regression analyses were performed on the data.

Results: In European Americans, the most significant findings were a protective association of the TLR9 +2848 GG genotype and a risk-enhancing association of the TLR9 TA haplotype with pustule formation; logistic regression showed a trend toward protection for the TLR9 +2848 GG genotype. In African Americans, logistic regression showed a protective effect for the IL10 -2849 AA genotype and a risk-enhancing effect for the IL10 AAC haplotype.

Conclusions: Variations in TLR9 and IL10 are associated with the outcome of H. ducreyi infection.

Keywords: Haemophilus ducreyi; chancroid; humans; immunogenetics; innate immunity; skin ulcers.

MeSH terms

  • Adult
  • Black or African American
  • Chancroid / genetics*
  • Chancroid / immunology
  • Cohort Studies
  • Female
  • Genetic Association Studies
  • Genotype
  • Haemophilus ducreyi / immunology*
  • Healthy Volunteers
  • Humans
  • Interleukin-10 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Real-Time Polymerase Chain Reaction
  • Toll-Like Receptor 9 / genetics*
  • United States
  • White People
  • Young Adult

Substances

  • IL10 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Interleukin-10