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WV002 Streptococcus pyogenes recruits collagen via surface bound fibronectin: a novel colonisation and immune evasion mechanism
Wissenschaftliches Programm 55. DGHM-Tagung 29. September-1. Oktober 2003 in Dresden Abstracts - Kurzvortr~ge
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Eukaryontische Krankheitserreger, Mikrobielle Pathogenit~it und Infektionsim rnunologie gerneinsarn zur ,,Wirt-Pathogen-Interaktion" Kurzvortr~ge Guest Speaker I m m u n e Evasion Reinhard WQrzner 1 1Institute of Hygiene and Social Medicine, Univ. of Innsbruck, Austria Virtually all pathogens invading the human body are attacked by the host immune system directly following entry and usually also during consecutive stages of disease, especially when they are in contact with blood. In order to escape or overcome immune defence most micro-organisms have developed an effective battery of specific strategies. As the innate immune system forms a very important part of the immune defence evading the interplay between complement and the phagocytic system plays a major role for the invader in order to survive the hostile environment within the host. The measures to avoid recognition and destruction by complement via complement-mediated attraction, opsonisation and activation of phagocytic cells, and lysis involves microbial molecules which are expressed on the surface or secreted into the near vicinity and can therefore by considered as virulence factors. Of all these highly sophisticated mechanisms employment of complement or its imitation (molecular mimicry) appear to be the most evolutionary elaborated.
Streptococcus pyogenes recruits collagen via surface bound fibronectin: a novel colonisation and i m m u n e evasion mechanism Talay, S.1; Dinkla, K.~; Rohde, M}; Chhatwal, G. ~ 1GBF-German Research Centre for Biotechnology; Microbial Pathogenesis and Vaccine Research This study aimed to characterise matrix assembly mechanisms on the surface of the human pathogen Streptococcus pyogenes. S. pyogenes isolates expressing the fibronectin binding adhesin and invasin SfbI were able to recruit collagen type IV via surfacebound fibronectin. Streptococcus gordonii expressing the fibronectin-binding repeat domain of S. pyogenes SfbI protein was equally potent in recruiting collagen, indicating that this domain was sufficient to promote fibronectin-mediated collagen-recruitment. Electron microscopical analysis of streptococci revealed that fibronectin-mediated collagen-recruitment led to matrix deposition on and between streptococcal cells, which induced the formation of large bacterial aggregates. Furthermore, collagen-recruiting streptococci were able to colonise collagen fibres, and were protected from adhering to human polymorph nuclear cells in the
http://www.dghm.org
96
Wissenschaftliches Programm 55. DGHM-Tagung 29. September-1. Oktober 2003 in Dresden Abstracts - Kurzvortr~ge
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presence of opsonising antibodies. Fibronectinmediated collagen-recruitment thus represents a novel aggregation, colonisation and immune ~ evasion mechanism of S. pyogenes.
Interaction between Neisseria meningitidis and human Dendritic Cells is strain-dependent and not mediated by major protein antigens of the bacterial surface Kurzai, 0.1, Schmitt, C.1; Claus, H } ; Vogel, U.1; Frosch, M.Z; Kolb-M~urer, A. 2
1University of WElrzburg; Institute of Hygiene and Microbiology N. meningitidis infection depends on the ability of the bacteria to cross the epithelial barrier of the oropharynx. Within this barrier, dendritic cells (DCs) are one of the first lines of defence, likely to play a major role in initiating an immune response. We have shown previously that phagocytosis of N. meningitidis by human DCs is efficient in unencapsulated strains. In contrast, expression of the capsule prevents adherence and phagocytosis of the bacteria. In this study, the function of major protein antigens of the bacterial outer membrane in DC - N. meningitidis interaction was examined for the hypervirulent clinical isolate MC58. In contrast to epithelial cells, the outer membrane proteins OpcA and OpaA did not mediate bacterial adhesion to the surface of DCs. In addition, expression of class I pill did not confer an adherent phenotype to unencapsulated N. meningitidis strains. Adherence of N. meningitidis to human dendritic cells could be partially inhibited by mannan and poly-T in some experiments, indicating a possible role for the macrophage mannose receptor and scavenger receptors in N. meningitidis recognition. However, the contribution of these receptors seemed to be highly variable for DCs from different donors. Furthermore, meningococci with different genetic backgrounds differed markedly with regard to their interaction with human DCs. The unencapsulated carriage isolate a710 (ST-136) did not display a higher affinity to dendritic cells than its encapsulated wild-type, a14 (ST-53), a constitutively unencapsulated carriage isolate, was also not recognized by DCs. Although the nature of the physical interaction between human DCs and N. meningitidis is not clear, it will be of significant interest to determine bacterial and cellular factors contributing to recognition of N. meningitidis. Given the central role of DCs in antigen presentation and T-cell activation, the inter-strain differences could significantly influence activation of the immune system.
http ://www. dg hm.org
97
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Eukaryontische Krankheitserreger, Mikrobielle Pathogenit~it und Infektionsim rnunologie gerneinsarn zur ,,Wirt-Pathogen-Interaktion" Kurzvortr~ge Guest Speaker I m m u n e Evasion Reinhard WQrzner 1 1Institute of Hygiene and Social Medicine, Univ. of Innsbruck, Austria Virtually all pathogens invading the human body are attacked by the host immune system directly following entry and usually also during consecutive stages of disease, especially when they are in contact with blood. In order to escape or overcome immune defence most micro-organisms have developed an effective battery of specific strategies. As the innate immune system forms a very important part of the immune defence evading the interplay between complement and the phagocytic system plays a major role for the invader in order to survive the hostile environment within the host. The measures to avoid recognition and destruction by complement via complement-mediated attraction, opsonisation and activation of phagocytic cells, and lysis involves microbial molecules which are expressed on the surface or secreted into the near vicinity and can therefore by considered as virulence factors. Of all these highly sophisticated mechanisms employment of complement or its imitation (molecular mimicry) appear to be the most evolutionary elaborated.
Streptococcus pyogenes recruits collagen via surface bound fibronectin: a novel colonisation and i m m u n e evasion mechanism Talay, S.1; Dinkla, K.~; Rohde, M}; Chhatwal, G. ~ 1GBF-German Research Centre for Biotechnology; Microbial Pathogenesis and Vaccine Research This study aimed to characterise matrix assembly mechanisms on the surface of the human pathogen Streptococcus pyogenes. S. pyogenes isolates expressing the fibronectin binding adhesin and invasin SfbI were able to recruit collagen type IV via surfacebound fibronectin. Streptococcus gordonii expressing the fibronectin-binding repeat domain of S. pyogenes SfbI protein was equally potent in recruiting collagen, indicating that this domain was sufficient to promote fibronectin-mediated collagen-recruitment. Electron microscopical analysis of streptococci revealed that fibronectin-mediated collagen-recruitment led to matrix deposition on and between streptococcal cells, which induced the formation of large bacterial aggregates. Furthermore, collagen-recruiting streptococci were able to colonise collagen fibres, and were protected from adhering to human polymorph nuclear cells in the
http://www.dghm.org
96
Wissenschaftliches Programm 55. DGHM-Tagung 29. September-1. Oktober 2003 in Dresden Abstracts - Kurzvortr~ge
GESE~I#C •C•£ g
,
;
presence of opsonising antibodies. Fibronectinmediated collagen-recruitment thus represents a novel aggregation, colonisation and immune ~ evasion mechanism of S. pyogenes.
Interaction between Neisseria meningitidis and human Dendritic Cells is strain-dependent and not mediated by major protein antigens of the bacterial surface Kurzai, 0.1, Schmitt, C.1; Claus, H } ; Vogel, U.1; Frosch, M.Z; Kolb-M~urer, A. 2
1University of WElrzburg; Institute of Hygiene and Microbiology N. meningitidis infection depends on the ability of the bacteria to cross the epithelial barrier of the oropharynx. Within this barrier, dendritic cells (DCs) are one of the first lines of defence, likely to play a major role in initiating an immune response. We have shown previously that phagocytosis of N. meningitidis by human DCs is efficient in unencapsulated strains. In contrast, expression of the capsule prevents adherence and phagocytosis of the bacteria. In this study, the function of major protein antigens of the bacterial outer membrane in DC - N. meningitidis interaction was examined for the hypervirulent clinical isolate MC58. In contrast to epithelial cells, the outer membrane proteins OpcA and OpaA did not mediate bacterial adhesion to the surface of DCs. In addition, expression of class I pill did not confer an adherent phenotype to unencapsulated N. meningitidis strains. Adherence of N. meningitidis to human dendritic cells could be partially inhibited by mannan and poly-T in some experiments, indicating a possible role for the macrophage mannose receptor and scavenger receptors in N. meningitidis recognition. However, the contribution of these receptors seemed to be highly variable for DCs from different donors. Furthermore, meningococci with different genetic backgrounds differed markedly with regard to their interaction with human DCs. The unencapsulated carriage isolate a710 (ST-136) did not display a higher affinity to dendritic cells than its encapsulated wild-type, a14 (ST-53), a constitutively unencapsulated carriage isolate, was also not recognized by DCs. Although the nature of the physical interaction between human DCs and N. meningitidis is not clear, it will be of significant interest to determine bacterial and cellular factors contributing to recognition of N. meningitidis. Given the central role of DCs in antigen presentation and T-cell activation, the inter-strain differences could significantly influence activation of the immune system.
http ://www. dg hm.org
97