Haemophilus ducreyiInfection 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-1α 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.

α‐MSH reduces the internalization of Staphylococcus aureus and down‐regulates HSP 70, integrins and cytokine expression in human keratinocyte cell lines

“…Keratinocytes are reported to produce pro‐inflammatory molecules, including IL‐8 and TNF‐α caused by various inflammatory stimuli, such as TNF, etc. (35,36).…”

Effects of staphylococci on cytokine production from human keratinocytes

“…Staphylococcus skin infection is characterized by the infiltration of numerous neutrophils within the epidermis. Neutrophils are known to play an important role in host defence against infection with various bacterial pathogens 1,2 . However, the precise mechanism of epidermal infiltration of neutrophils during skin infection with staphylococci is not well understood and the factors regulating the neutrophil recruitment are yet to be determined.…”

Chancroid: contemporary appraisal

“…This has fascinated investigators in to forming a detailed profile, including the characters of this organism, worldwide. 2,5-10, [39][40][41][42][43][44] The disease affects both males and females, with the former outnumbering the latter. The male to female ratio was found to be 27 : 1 in India, signifying that women are asymptomatic carriers (reservoir) of the organism.…”

“…This has fascinated investigators in to forming a detailed profile, including the characters, of this organism worldwide. 2,5-10, [39][40][41][42][43][44] The potential virulence factors in this organism, namely lipo-oligo-saccharide (LOS), pili, extracellular toxins, and hemolysin, 39,[46][47][48][49] have been identified. Several useful animal models, rabbits, primates, and pigs, as well as human volunteers have been employed for defining the characteristics of this fastidious bacteria.…”

“…53,54 Viable H. ducreyi along with LOS, cytolethal distending toxin, fine tangled pili and cells, and associated hemolysis, have also been identified in the lesions. 39,[46][47][48][49]56 An artificial skin model has been developed using neonatal foreskin fibroblasts and keratinocytes in a coculture system composed of dermal, epidermal and stratum corneum layers anchored to a nylon mesh support, and the affects of virulent H. ducreyi have been thoroughly investigated. 39 As with other organisms, the virulence of H. ducreyi is probably multifactorial and is dependent on the presence, relative expression, and cell range of several different virulence factors.…”