title: Haemophilus ducreyi infection causes basal keratinocyte cytotoxicity and elicits a unique cytokine induction pattern in an In vitro human skin model.
abstract: Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid. Predominantly a cutaneous pathogen, H. ducreyi is present in chancroid ulcers that are characterized by extensive neutrophil accumulation in intraepidermal lesions accompanied by a mononuclear infiltrate in the dermis. We used an in vitro human skin model composed of foreskin fibroblasts and keratinocytes to examine host skin cell interactions with H. ducreyi 35000. Bacteria replicated and persisted in artificial skin for at least 14 days. We observed H. ducreyi inside suprabasal keratinocytes using transmission electron microscopy. Although no bacteria were seen in the basal keratinocyte region, these cells were disrupted in infected cocultures. H. ducreyi infection stimulated increased secretion of interleukin-6 (IL-6) and IL-8 by skin cells. Conversely, tumor necrosis factor alpha and IL-1alpha levels were not elevated. IL-8 produced in response to H. ducreyi infection may be involved in recruiting polymorphonuclear leukocytes and other inflammatory cells, thereby contributing to the tissue necrosis and ulcer formation characteristic of chancroid.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA. mmhobbs@med.unc.edu
authors.forename: M M
authors.initials: MM
authors.lastname: Hobbs
authors.forename: T R
authors.initials: TR
authors.lastname: Paul
authors.forename: P B
authors.initials: PB
authors.lastname: Wyrick
authors.forename: T H
authors.initials: TH
authors.lastname: Kawula
mesh_terms: D002478:Cells, Cultured; D002602:Chancroid / Q000209:etiology; D016207:Cytokines / Q000378:metabolism*; D006191:Haemophilus ducreyi / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000473:pathology*; D008297:Male; D012867:Skin / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha