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



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.



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.



Variations in TLR9 and IL10 are associated with the outcome of H. ducreyi infection.
Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam.
Martin
M
Singer
Department of Microbiology and Immunology.
Wei
W
Li
Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam Institute for Public Health Genomics, Department of Genetics and Cell Biology, School for Oncology and Developmental Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands.
Servaas A
SA
Morré
Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam.
Sander
S
Ouburg
Department of Microbiology and Immunology Departments of Medicine Pathology and Laboratory Medicine Center for Immunobiology, Indiana University School of Medicine, Indiana University, Indianapolis.
Stanley M
SM
Spinola
D000328:Adult; D001741:Black or African American; D002602:Chancroid / Q000235:genetics* / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006191:Haemophilus ducreyi / Q000276:immunology*; D064368:Healthy Volunteers; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D014481:United States; D044465:White People; D055815:Young Adult
C508609:IL10 protein, human; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D016753:Interleukin-10
Haemophilus ducreyi; chancroid; humans; immunogenetics; innate immunity; skin ulcers