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Interactions of Haemophilus ducreyi and purified cytolethal distending toxin with human monocyte-derived dendritic cells, macrophages and CD4+ T cells.

Författare och institution:
Tingting Xu (Institutionen för medicinsk mikrobiologi och immunologi); Annika Lundqvist (Institutionen för medicinsk mikrobiologi och immunologi); Hinda J Ahmed (Institutionen för medicinsk mikrobiologi och immunologi); Kristina Eriksson (Institutionen för invärtesmedicin, Avdelningen för reumatologi och inflammationsforskning); Yonghong Yang (-); Teresa Lagergård (Institutionen för medicinsk mikrobiologi och immunologi)
Publicerad i:
Microbes and infection / Institut Pasteur, 6 ( 13 ) s. 1171-81
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
To evaluate the early stages of the host response to chancroid bacterium Haemophilus ducreyi, we investigated the in vitro responses of monocyte-derived dendritic cells (DCs) and macrophages (MQs) to this pathogen and Haemophilus influenzae. The phagocytic activities and pro-inflammatory cytokine secretion profiles of the antigen-presenting cells (APCs) were analyzed after exposure to gentamycin-killed bacteria, H. ducreyi lipooligosaccharide (LOS), and purified cytolethal distending toxin (HdCDT). T-cell proliferation and cytokine release were examined after co-culturing isolated autologous CD4+ T cells with antigen-pulsed APCs. Both the DCs and MQs phagocytosed H. ducreyi and H. influenzae, as estimated by flow cytometry. All of the strains induced APC secretion of TNF-alpha, IL-6, IL-8, and IL-12, as measured by ELISA. Other human cells, particularly endothelial cells and fibroblasts, also produced cytokines when stimulated with these bacteria. Purified LOS at concentration 1 microg/ml induced two to threefold lower levels of cytokines than the whole bacteria, which indicates that other components are involved in immune activation. HdCDT inhibited partially the production of the aforementioned cytokines. High levels of IFN-gamma, but not of IL-4 and IL-13, were secreted by T cells after activation by either DCs or MQs that were pre-exposed to bacteria, indicating the Th1 nature of the immune response. The levels of T-cell proliferation induced by H. ducreyi were lower than those induced by H. influenzae. HdCDT-treated APCs did not display cytokine responses or T-cell proliferation. These results indicate that HdCDT intoxication, which results in progressive apoptosis of APCs, may hamper early stage immune responses.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Apoptosis, Bacterial Toxins, toxicity, CD4-Positive T-Lymphocytes, immunology, Cell Proliferation, Cells, Cultured, Dendritic Cells, immunology, Endothelial Cells, microbiology, Fibroblasts, microbiology, Haemophilus ducreyi, immunology, Humans, Interferon Type II, analysis, Interleukin-12, analysis, Interleukin-13, analysis, Interleukin-4, analysis, Interleukin-6, analysis, Interleukin-8, analysis, Lymphocyte Activation, Macrophages, immunology, Phagocytosis, Tumor Necrosis Factor-alpha, analysis
Postens nummer:
Posten skapad:
2007-10-12 14:35
Posten ändrad:
2010-01-26 12:48

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