An Immunohistochemical Analysis of Naturally Occurring Chancroid

King, Roy; Gough, Julie E.; Ronald, Allan; Nasio, James M.; Ndinya-Achola, Jackoniah O.; Plummer, Frank; Wilkins, John A.

doi:10.1093/infdis/174.2.427

Cited by 45 publications

(34 citation statements)

References 12 publications

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“…In mock-immunized animals challenged with either strain (Fig. 1B6 and 8), there was a dense infiltrate of neutrophils and the epidermal-dermal border was completely destroyed, which left the dermis exposed, similar to previous results (1) and comparable to natural and experimental infection in humans (34,56). In the nHgbA I -immunized heterologous challenge group (Fig.…”

Section: Resultssupporting

confidence: 89%

Immunization with the Haemophilus ducreyi Hemoglobin Receptor HgbA with Adjuvant Monophosphoryl Lipid A Protects Swine from a Homologous but Not a Heterologous Challenge

et al. 2010

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Haemophilus ducreyi, the etiological agent of chancroid, has a strict requirement for heme, which it acquires from its only natural host, humans. Previously, we showed that a vaccine preparation containing the native hemoglobin receptor HgbA purified from H. ducreyi class I strain 35000HP (nHgbA I ) and administered with Freund's adjuvant provided complete protection against a homologous challenge. In the current study, we investigated whether nHgbA I dispensed with monophosphoryl lipid A (MPL), an adjuvant approved for use in humans, offered protection against a challenge with H. ducreyi strain 35000HP expressing either class I or class II HgbA (35000HPhgbA I and 35000HPhgbA II , respectively). Pigs immunized with the nHgbA I /MPL vaccine were protected against a challenge from homologous H. ducreyi strain 35000HPhgbA I but not heterologous strain 35000HPhgbA II , as evidenced by the isolation of only strain 35000HPhgbA II from nHgbA I -immunized pigs. Furthermore, histological analysis of the lesions showed striking differences between mock-immunized and nHgbA I -immunized animals challenged with strains 35000HPhgbA I but not those challenged with strain 35000HPhgbA II . Mock-immunized pigs were not protected from a challenge by either strain. The enzyme-linked immunosorbent assay (ELISA) activity of the nHgbA I /MPL antiserum was lower than the activity of antiserum from animals immunized with the nHgbA I /Freund's vaccine; however, anti-nHgbA I from both studies bound whole cells of 35000HPhgbA I better than 35000HPhgbA II and partially blocked hemoglobin binding to nHgbA I . In conclusion, despite eliciting lower antibody ELISA activity than the nHgbA I /Freund's, the nHgbA I /MPL vaccine provided protection against a challenge with homologous but not heterologous H. ducreyi, suggesting that a bivalent HgbA vaccine may be needed.

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Section: Resultssupporting

confidence: 89%

Immunization with the Haemophilus ducreyi Hemoglobin Receptor HgbA with Adjuvant Monophosphoryl Lipid A Protects Swine from a Homologous but Not a Heterologous Challenge

et al. 2010

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“…ducreyi has been shown to associate with human granulocytes and macrophages in chancroidal lesions that occur naturally (31,37) and in the human challenge model of infection (8,10,49). At least during the early stages of experimental infection (i.e., through pustule development), H. ducreyi can be found associated with PMNs and macrophages but not with T cells, Langerhans' cells, or fibroblasts (8).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Phagocytosis byHaemophilus ducreyiRequires Expression of the LspA1 and LspA2 Proteins

2003

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Haemophilus ducreyi previously has been shown to inhibit the phagocytosis of both secondary targets and itself by certain cells in vitro. Wild-type H. ducreyi strain 35000HP contains two genes, lspA1 and lspA2, whose encoded protein products are predicted to be 456 and 543 kDa, respectively. An isogenic mutant of H. ducreyi 35000HP with inactivated lspA1 and lspA2 genes has been shown to exhibit substantially decreased virulence in the temperature-dependent rabbit model for chancroid. This lspA1 lspA2 mutant was tested for its ability to inhibit phagocytosis of immunoglobulin G-opsonized particles by differentiated HL-60 and U-937 cells and by J774A.1 cells. The wild-type strain H. ducreyi 35000HP readily inhibited phagocytosis, whereas the lspA1 lspA2 mutant was unable to inhibit phagocytosis. Similarly, the wild-type strain was resistant to phagocytosis, whereas the lspA1 lspA2 mutant was readily engulfed by phagocytes. This inhibitory effect of wild-type H. ducreyi on phagocytic activity was primarily associated with live bacterial cells but could also be found, under certain conditions, in concentrated H. ducreyi culture supernatant fluids that lacked detectable outer membrane fragments. Both the wild-type strain and the lspA1 lspA2 mutant attached to phagocytes at similar levels. These results indicate that the LspA1 and LspA2 proteins of H. ducreyi are involved, directly or indirectly, in the antiphagocytic activity of this pathogen, and they provide a possible explanation for the greatly reduced virulence of the lspA1 lspA2 mutant.

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“…In vivo, H. ducreyi is found in association with macrophages in naturally acquired chancroid lesions and in the human experimental infection model (2,25,26,31,42,43). To under- stand the mechanisms by which H. ducreyi persists and survives in the presence of these phagocytes, we explored the in vitro interactions of H. ducreyi with the human macrophage-like cell line, U-937.…”

Section: Discussionmentioning

confidence: 99%

“…Chancroid lesions involve cells of the epidermis and dermis and contain an immune cell infiltrate consisting of polymorphonuclear leukocytes (PMNs), T cells, and macrophages (2,25,26,42,43). Despite this immune cell infiltrate, viable H. ducreyi can be isolated from these ulcers weeks or months after initial infection (31).…”

mentioning

confidence: 99%

Haemophilus ducreyi Inhibits Phagocytosis by U-937 Cells, a Human Macrophage-Like Cell Line

2001

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Haemophilus ducreyi is a gram-negative obligate human pathogen that causes the genital ulcer disease chancroid. Chancroid lesions are deep necrotic ulcers with an immune cell infiltrate that includes macrophages. Despite the presence of these phagocytic cells, chancroid ulcers can persist for months and live H. ducreyi can be isolated from these lesions. To analyze the interaction of H. ducreyi with macrophages, we investigated the ability of H. ducreyi strain 35000 to adhere to, invade, and survive within U-937 cells, a human macrophage-like cell line. We found that although H. ducreyi strain 35000 adhered efficiently to U-937 cells, few bacteria were internalized, suggesting that H. ducreyi avoids phagocytosis by human macrophages. The few bacteria that were phagocytosed in these experiments were rapidly killed. We also found that H. ducreyi inhibits the phagocytosis of a secondary target (opsonized sheep red blood cells). Antiphagocytic activity was found in logarithmic, stationary-phase, and plate-grown cultures and was associated with whole, live bacteria but not with heat-killed cultures, sonicates, or culture supernatants. Phagocytosis was significantly inhibited after a 15-min exposure to H. ducreyi, and a multiplicity of infection of approximately 1 CFU per macrophage was sufficient to cause a significant reduction in phagocytosis by U-937 cells. Finally, all of nine H. ducreyi strains tested were antiphagocytic, suggesting that this is a common virulence mechanism for this organism. This finding suggests a mechanism by which H. ducreyi avoids killing and clearance by macrophages in chancroid lesions and inguinal lymph nodes.

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An Immunohistochemical Analysis of Naturally Occurring Chancroid

Cited by 45 publications

References 12 publications

Immunization with the Haemophilus ducreyi Hemoglobin Receptor HgbA with Adjuvant Monophosphoryl Lipid A Protects Swine from a Homologous but Not a Heterologous Challenge

Immunization with the Haemophilus ducreyi Hemoglobin Receptor HgbA with Adjuvant Monophosphoryl Lipid A Protects Swine from a Homologous but Not a Heterologous Challenge

Inhibition of Phagocytosis byHaemophilus ducreyiRequires Expression of the LspA1 and LspA2 Proteins

Haemophilus ducreyi Inhibits Phagocytosis by U-937 Cells, a Human Macrophage-Like Cell Line

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