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University of Helsinki

1. Teirilä, Laura. Activation of the Inflammatory Response by Fungal Components.

Degree: Haartman Institute; Finnish Institute of Occupational Health, Helsinki, 2017, University of Helsinki

Fungi are associated with a wide range of diseases from superficial skin syndromes to invasive life-threating conditions. Furthermore, exposure to non-infectious fungal components in the context of agricultural work or in water-damaged houses has been associated to illnesses in the respiratory tract. The inadequate knowledge of the immune mechanisms behind these illnesses has triggered an intense research effort attempting to understand how fungi can activate the defense mechanisms of immune system. This thesis focused on the inflammation triggered by the fungal components. The inflammatory response and related mechanisms were studied in vitro in the key defense cell of innate immunity, the macrophage, which were treated with a central cell wall component of fungi, (1,3)- β-glucan. One major outcome of this thesis was the finding that β-glucan evokes a strong pro-inflammatory response via the IL-1 family cytokines in human macrophages. These cytokines are crucial mediators of inflammation, thus their secretion is highly regulated. Our study showed that β-glucan, on its own, could cause the efficient secretion of functional IL-1β and other mediators of inflammation via unconventional secretion pathways by activating both dectin-1 signaling pathway and NLRP3 inflammasome. This β-glucan-induced protein secretion via unconventional pathways was suppressed by inhibition of inflammasome activity or by preventing the process of autophagy. Furthermore, the well-known myeloid cell growth factor, granulocyte-macrophage colony-stimulating factor seems to be one of the factors boosting the β-glucan-triggered inflammatory response of macrophages. In an attempt to obtain direct information about conditions caused by the exposure to fungal and other microbial particles, we characterized the proteomic changes present in the bronchoalveolar lavage obtained from patients suffering illnesses associated with exposure to inhaled microbial particles. The proteomic profiles of hypersensitivity pneumonitis (HP) were different from the profile of damp building-related illness (DBRI), indicating that these conditions are not closely associated. However, the increase in the levels of two well-known markers of inflammation was observed in both HP and DBRI, evidence for the activation of inflammatory mechanisms in both of these conditions. This thesis provides novel knowledge concerning the inflammatory response and related mechanisms triggered by fungal components. These results may help to clarify the mechanisms behind the inflammatory symptoms experienced by individuals with fungal infections or exposure to fungal particles and will provide future tools for the treatment of fungal-related disorders.

Sienet aiheuttavat monenlaisia tauteja vaihdellen ihon pintainfektioista hengenvaarallisiin syviin sieni-infektioihin. Sienialtistuksesta johtuvaa oireilua tavataan myös henkilöillä, jotka ovat altistuneet sienen rakennekomponenteille tehdessään maataloustöitä homeisen heinän parissa, tai oleskellessaan rakennuksissa, joissa on todettu…

Subjects/Keywords: lääketiede/biotieteet; lääketiede/biotieteet

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Teirilä, L. (2017). Activation of the Inflammatory Response by Fungal Components. (Doctoral Dissertation). University of Helsinki. Retrieved from http://hdl.handle.net/10138/175899

Chicago Manual of Style (16th Edition):

Teirilä, Laura. “Activation of the Inflammatory Response by Fungal Components.” 2017. Doctoral Dissertation, University of Helsinki. Accessed May 28, 2017. http://hdl.handle.net/10138/175899.

MLA Handbook (7th Edition):

Teirilä, Laura. “Activation of the Inflammatory Response by Fungal Components.” 2017. Web. 28 May 2017.

Vancouver:

Teirilä L. Activation of the Inflammatory Response by Fungal Components. [Internet] [Doctoral dissertation]. University of Helsinki; 2017. [cited 2017 May 28]. Available from: http://hdl.handle.net/10138/175899.

Council of Science Editors:

Teirilä L. Activation of the Inflammatory Response by Fungal Components. [Doctoral Dissertation]. University of Helsinki; 2017. Available from: http://hdl.handle.net/10138/175899

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