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Infection and Immunity, December 2007, p. 5678-5685, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00702-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Haemophilus ducreyi Partially Activates Human Myeloid Dendritic Cells{triangledown}

Keith E. Banks,1 Tricia L. Humphreys,1,{dagger} Wei Li,1 Barry P. Katz,1 David S. Wilkes,1,2,4 and Stanley M. Spinola1,2,3,4*

Departments of Medicine,1 Microbiology and Immunology,2 Pathology and Laboratory Medicine,3 Center for Immunobiology, Indiana University, School of Medicine, Indianapolis, Indiana 462024

Received 23 May 2007/ Returned for modification 10 July 2007/ Accepted 25 September 2007

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.

* Corresponding author. Mailing address: 435 Emerson Hall, 545 Barnhill Drive, Indianapolis, IN 46202-5124. Phone: (317) 274-1427. Fax: (317) 274-1587. E-mail: sspinola{at}iupui.edu

{triangledown} Published ahead of print on 8 October 2007.

Editor: J. L. Flynn

{dagger} Present address: Department of Biology, Grinnell College, Grinnell, IA 50112.

Infection and Immunity, December 2007, p. 5678-5685, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00702-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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  • Humphreys, T. L., Li, L., Li, X., Janowicz, D. M., Fortney, K. R., Zhao, Q., Li, W., McClintick, J., Katz, B. P., Wilkes, D. S., Edenberg, H. J., Spinola, S. M. (2007). Dysregulated Immune Profiles for Skin and Dendritic Cells Are Associated with Increased Host Susceptibility to Haemophilus ducreyi Infection in Human Volunteers. Infect. Immun. 75: 5686-5697 [Abstract] [Full Text]  


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