January 2003

Project leader: ILKKA JULKUNEN,
Department of Microbiology, National Public Health Institut, Mannerheimintie 166, 00300 Helsinki. Tel. 358-9-47448372. ilkka.julkunen@ktl.fi

Other project leaders of the consortium: Timo Korhonen, Department of Biosciences, Division of General Microbiology, Viikinkaari 9, P.O.Box 00014 University of Helsinki. Timo.korhonen@helsinki.fi

Doctoral students:
MSc Ville Veckman, National Public Health Institute, Helsinki, ville.veckman@ktl.fi
MSc Pamela Österlund, National Public Health Institute, Helsinki, pamela.osterlund@ktl.fi
MSc Anne Lehtonen, National Public Health Institute, Helsinki, anne.lehtonen@ktl.fi
MSc Mari Strengell, National Public Health Institute, Helsinki, mari.strengell@ktl.fi
BSc Jukka Sirén, National Public Health Institute, Helsinki, jukka.siren@ktl.fi
BSc Taija Pietilä, National Public Health Institute, Helsinki, taija.pietila@ktl.fi
MSc Sanna Edelman, Department of Biosciences, University of Helsinki, sanna.edelman@helsinki.fi
MSc Maini Kukkonen, Department of Biosciences, University of Helsinki, maini.kukkonen@helsinki.fi
MSc Jenni Antikainen, Department of Biosciences, University of Helsinki, jenni.antikainen@helsinki.fi
MSc Marjo Suomalainen, Dept of Biosciences, University of Helsinki, marjo.suomalainen@helsinki.fi
MSc Leandro Lobo, Department of Biosciences, University of Helsinki, leandro.lobo@helsinki.fi
BSc Päivi Kyllönen, Department of Biosciences, University of Helsinki, paivi.kyllonen@helsinki.fi

Other Researchers:
PhD, docent Sampsa Matikainen, National Public Health Institute, Helsinki, sampsa.matikainen@ktl.fi
PhD Minja Miettinen, National Public Health Institute, Helsinki, minja.miettinen@ktl.fi
PhD Kaarina Lähteenmäki, Department of Biosciences, University of Helsinki, kaarina.lahteenmaki@helsinki.fi
PhD, docent Mikael Rhen, Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, mikael.rhen@mtc.ki.se

Abstract
Despite the ability of epithelial cells to recognise and respond to conserved bacterial components, and to both accommodate and communicate with professional phagocytic cells, the mucosal membrane confronts the normal flora with apparently no pathological consequences. Many pathogens can remain as asymptomatic colonisers, whereas others activate hosts innate and inflammatory reactions. This project aims at defining factors and mechanisms that cause the host to regulate its reactions to asymptomatic colonisers and pathogenic bacteria. Many infectious diseases and especially their symptoms, can result from inflammatory responses caused by the pathogen at the epithelial surface. For these host-pathogen interactions, the inflammatory response appears to be necessary for the pathogen to cause an infection. Host cells respond to conserved bacterial components such as lipopolysaccharide (LPS) and peptidoclycan via activation of Toll-like receptors (TLRs) that stimulate activation of multiple transcription factor systems and activate host cell apoptosis, proteolytic cascades, innate immune responses and cytokine production. Some bacteria, like salmonella can abrogate inflammatory reactions by blocking the activation of e.g. NF-k B transcription factors. This suggest that bacteria, besides activating host innate defence responses, also have the ability to downregulate the activation of host immune system. This project will define and characterise bacterial factors that regulate the interaction between the host and a potential pathogen in carrier states of an infection. In this research project we focus on bacterial factors that manipulate innate recognition and subsequent signal transduction in the epithelial or professional phagocytic cell. As model pathogens we have chosen salmonella, streptococcus and lactobacillus. Using cell culture models, we aim to define how bacterial proteins, alterations in surface structures, and novel interactions between virulence factors (PgtE) and LPS affect bacterial adaptation to host cells and how this adaptation is connected to reduced virulence.

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