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The role of macrophages in the regulation of systemic metabolism in Drosophila
KREJČOVÁ, Gabriela
Macrophages are immensely versatile cells in the mammalian body, fulfilling roles ranging from protection against pathogenic intruders and engulfing apoptotic cells to morphogenesis and maintenance of tissue homeostasis. This impressive functional versatility may be achieved due to plasticity of macrophage cellular metabolism called metabolic polarization. The adoption of different polarization phenotypes by macrophages determines their function and is essential for the health of the organism. Nonetheless, if the cells lose their metabolic plasticity or polarize inadequately to a particular situation, it can lead to the development of chronic pathological states such as metabolic syndrome. Metabolic polarization of immune cells is thus a key factor in determining whether macrophage function within the organism will be adaptive or pathological. Despite Drosophila melanogaster represents a major model organism for immunological studies, the metabolic setup of activated immune cells has not been addressed up to now. The results of this thesis document that Drosophila immune cells undergo metabolic polarization toward aerobic glycolysis when challenged by extracellular bacteria. Mammals alike, this cellular metabolic switch is regulated by the transcription factor HIF1, thus documenting the conservation of this process between insects and vertebrates. Furthermore, we show that the adoption of aerobic glycolysis is directly linked to the production of the signaling factor IMPL2, which induces the mobilization of lipid stores from the fat body via the silencing of insulin signaling. By this mechanism, immune cells secure sufficient nutrients for successful elimination of the pathogen. Moreover, the mammalian ImpL2 homolog IGFBP7 appears to act analogously in the mammalian liver not only during severe infectious states but also in the liver of obese individuals. While such macrophage activity in regulating systemic metabolism is beneficial to the host during bacterial infection, it becomes maladaptive when chronically activated. Further evidence for a metabolism-regulatory role of immune cells has been found during insect metamorphosis and early post-metamorphic development. This thesis documents that during this period, macrophages infiltrate and engulf the histolyzing larval fat body and convert nutrients into storage peptides and lipoproteins. Subsequently, these nutrients are exploited by the maturing adult structures.
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Wingless/Notch crosstalk in Drosophila melanogaster
Hajšmanová, Hana ; Mašek, Jan (advisor) ; Macůrková, Marie (referee)
Fundamental for the existence of multicellular organisms is the presence signalling pathways, complex biochemical cascades, allowing reciprocal communication amongst the cells. Both Notch and Wnt pathways are crucial for embryonic development and their deregulation leads to many severe diseases. Decades of research, largely based on model organism D. melanogaster, showed that components of these pathways do not function strictly separately but on contrary interact with each other (crosstalk). This phenomenon is explored only to a lesser extent in mammals. The aim of this thesis is to recapitulate existing findings of Wnt/ Notch crosstalk in D. melanogaster and outline where crosstalk could play a role in mammals.
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