title: Haemophilus ducreyi partially activates human myeloid dendritic cells.
abstract: Dendritic cells (DC) orchestrate innate and adaptive immune responses to bacteria. How Haemophilus ducreyi, which causes genital ulcers and regional lymphadenitis, interacts with DC is unknown. H. ducreyi evades uptake by polymorphonuclear leukocyte and macrophage-like cell lines by secreting LspA1 and LspA2. Many H. ducreyi strains express cytolethal distending toxin (CDT), and recombinant CDT causes apoptosis of DC in vitro. Here, we examined interactions between DC and H. ducreyi 35000HP, which produces LspA1, LspA2, and CDT. In human volunteers infected with 35000HP, the ratio of myeloid DC to plasmacytoid DC was 2.8:1 in lesions, compared to a ratio of 1:1 in peripheral blood. Using myeloid DC derived from monocytes as surrogates for lesional DC, we found that DC infected with 35000HP remained as viable as uninfected DC for up to 48 h. Gentamicin protection and confocal microscopy assays demonstrated that DC ingested and killed 35000HP, but killing was incomplete at 48 h. The expression of LspA1 and LspA2 did not inhibit the uptake of H. ducreyi, despite inactivating Src kinases. Infection of DC with live 35000HP caused less cell surface marker activation than infection with heat-killed 35000HP and lipopolysaccharide (LPS) and inhibited maturation by LPS. However, infection of DC with live bacteria caused the secretion of significantly higher levels of interleukin-6 and tumor necrosis factor alpha than infection with heat-killed bacteria and LPS. The survival of H. ducreyi in DC may provide a mechanism by which the organism traffics to lymph nodes. Partial activation of DC may abrogate the establishment of a full Th1 response and an environment that promotes phagocytosis.
authors.affiliation: Department of Medicine, Center for Immunobiology, Indiana University, School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Keith E
authors.initials: KE
authors.lastname: Banks
authors.forename: Tricia L
authors.initials: TL
authors.lastname: Humphreys
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Barry P
authors.initials: BP
authors.lastname: Katz
authors.forename: David S
authors.initials: DS
authors.lastname: Wilkes
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Spinola
mesh_terms: D000328:Adult; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D002602:Chancroid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D005260:Female; D006191:Haemophilus ducreyi / Q000276:immunology*; D006801:Humans; D037102:Lectins / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D008297:Male; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis / Q000502:physiology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D037102:Lectins; C115859:LspA1 protein, Haemophilus ducreyi; C115860:LspA2 protein, Haemophilus ducreyi; D019061:src-Family Kinases