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Selected Publication:
Budiman, H.
Factors involved in the phagocytosis of Streptococcus pneumoniae by macrophages
[ Dissertation ] Medical University of Graz; 2003. pp.
- Authors Med Uni Graz:
- Advisor:
- Wenisch Christoph
- Altmetrics:
- Abstract:
- Part I: Streptococcus pneumoniae is a serious bacterial pathogen causing pneumonia, bacteremia and meningitis. Macrophages are critical components of the immune defense against bacterial infection, expressing a broad spectrum of plasma membrane receptors, which mediate recognition and internalization of microorganisms. Phagocytosis of bacteria by macrophages is a complex process in which molecules on the surface of the bacterium, serum proteins and receptors on the surface of the phagocytes are involved. So far it is largely unknown, which of these receptors and serum factors are involved in the uptake of S.pneumoniae. In the present study we studied the role of Fcy-Receptors (FcgammaRs9, complement receptor 3 (CR3) and serum factors in the phagocytosis of S.pneumoniae by macrophages. Phagocytosis was investigated in vitro with macrophage-like cell-lines as model for tissue macrophages and heat mouse serum is not essential for the phagocytosis by macrophages but is able to increase the amount of phagocytosis by macrophages bacteria. Furthermore, both CR3 and FcgammaRs were able to improve the phagocytic process, implying that both play a vital role in the uptake of S. pneumoniae. Part II: Toll-like receptors (TLRs) are key players of the innate immune response that sense the invasion of pathogens by detecting specific components of bacterial, viral and fungal pathogens. It has been shown, that exposure of macrophages to lipopolysaccharide (LPS), a TLR4 ligand, induces a state of hyporesponsiveness to subsequent stimulation with LPS, known as LPS tolerance. This phenomenon has also been shown for other PAMPs like lipoteichoic acid (LTA) and CpG DNA. Thus inductin of hyporesponsiveness in macrophages has been well studied at cytokine level, but little is known about the uptake of the whole bacterium. Therefore, we investigated whether phagocytosis of S.pneeumoniae by macrophages was altered after exposure to LPS and other TLR ligands including LTA, flagellin or CpG oligonculeotides. Phagocytosis of prestimulated cells was investigated in vitro with macrophage-like cell-lines as model for tissue macrophages and heat killed bacteria that were fluorescently labelled. Our results demonstrated, that cells pretreated with LPS, LTA and CpG did not show a lower, but an increased amount of phagocytosis, when subsequently challenged with S.pneumoniae. Furthermore, we investigated the role of CR3 upregulation after stimulatioin.