Inhibition of phagocytosis by Haemophilus ducreyi requires expression of the LspA1 and LspA2 proteins.
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.
D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004912:Erythrocytes / Q000276:immunology; D015870:Gene Expression; D005798:Genes, Bacterial; D018922:HL-60 Cells; D006191:Haemophilus ducreyi / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D006388:Hemagglutinins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D037102:Lectins; D051379:Mice; D008863:Microspheres; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis; D012756:Sheep; D013194:Staining and Labeling; D020298:U937 Cells
D001426:Bacterial Proteins; D006388:Hemagglutinins; D037102:Lectins; C115859:LspA1 protein, Haemophilus ducreyi; C115860:LspA2 protein, Haemophilus ducreyi; D009895:Opsonin Proteins