Immunopathogenesis ofHaemophilus ducreyiInfection (Chancroid)

Haemophilus ducreyi-Induced Interleukin-10 Promotes a Mixed M1 and M2 Activation Program in Human Macrophages

“…Papules form within 24 h of inoculation and either spontaneously resolve or evolve into pustules within 2 to 5 days, mimicking the early stages of natural infection. The cutaneous immune response in experimental infection consists of neutrophils, macrophages, myeloid dendritic cells (DC), NK cells, effector/memory CD4 and CD8 T cells, and FOXP3 ϩ regulatory T cells (5,25,26,46). Experimental pustules and natural ulcers are identical histologically and represent immunological failure.…”

“…To study the immunopathogenesis of H. ducreyi infection, we developed a human challenge model in which the skin of the upper arm of healthy adult volunteers is inoculated with H. ducreyi strain 35000HP or its derivatives (21,46,47). Papules form within 24 h of inoculation and either spontaneously resolve or evolve into pustules within 2 to 5 days, mimicking the early stages of natural infection.…”

A CdtA-CdtC Complex Can Block Killing of HeLa Cells by Haemophilus ducreyi Cytolethal Distending Toxin

“…While the mechanism(s) by which this gram-negative bacterium causes genital ulceration remains to be determined (31), it has been established that this pathogen produces at least two toxins. The first of these is a cytotoxin with hemolytic activity (20,21); killing of human cells in vitro by this hemolysin requires direct contact between the bacterium and the eukaryotic cells (2,19).…”

Evolution of the Cutaneous Immune Response to Experimental Haemophilus ducreyi Infection and Its Relevance to HIV-1 Acquisition

“…In experimental infection, H. ducreyi associates with the polymorphonuclear leukocytes in the pustule and with macrophages at the base of the pustule, but is not taken up by the phagocytes (23). By escaping phagocytic killing, the bacteria sustain the immune response that most likely damages the skin (22). Although the immunohistopathology of experimental and natural infection is well described, no quantitative studies that address kinetics of cell recruitment have been performed.…”

“…For subject safety, infection is not allowed to progress to ulcers. The model is useful in that it mimics the first 2 wk of an infection that in nature is probably present for 3-6 wk before patients with ulcers seek treatment (22).…”