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

Martin Singer, Wei Li, Servaas A. Morre, Sander Ouburg, Stanley Spinola

Research output: Contribution to journalArticle

1 Citation (Scopus)

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. χ2 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.

Original languageEnglish (US)
Pages (from-to)489-495
Number of pages7
JournalJournal of Infectious Diseases
Volume214
Issue number3
DOIs
StatePublished - Aug 1 2016

Fingerprint

Haemophilus ducreyi
Haemophilus Infections
Interleukin-10
Volunteers
Logistic Models
Genotype
Haplotypes
Single Nucleotide Polymorphism
Immunogenetics
Infection
African Americans
Real-Time Polymerase Chain Reaction
Regression Analysis
Cytokines
DNA
Genes

Keywords

  • chancroid
  • Haemophilus ducreyi
  • humans
  • immunogenetics
  • innate immunity
  • skin ulcers

ASJC Scopus subject areas

  • Immunology and Allergy
  • Medicine(all)
  • Infectious Diseases

Cite this

Host Polymorphisms in TLR9 and IL10 Are Associated with the Outcomes of Experimental Haemophilus ducreyi Infection in Human Volunteers. / Singer, Martin; Li, Wei; Morre, Servaas A.; Ouburg, Sander; Spinola, Stanley.

In: Journal of Infectious Diseases, Vol. 214, No. 3, 01.08.2016, p. 489-495.

Research output: Contribution to journalArticle

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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. χ2 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.",
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