Project A7

Role and targeting of bioactive lipid mediators in Aspergillus fumigatus - innate immune cell interactions

Project A7 focusses on lipid mediators (LMs) that control inflammation triggered by fungal infections. A7 will elucidate the mechanisms how A. fumigatus modulates LM networks in the host and how LM derivatives contribute to the deleterious impact of the fungus or help the host to resolve the infection. We will also define at which stage specialized pro-resolving mediators (SPMs) impact fungal infections, which immune cells are involved besides neutrophils, in which cells LM production is controlled by A. fumigatus and whether secondary metabolites other than gliotoxin play a modulatory role.

Figure: Graphical abstract of this project with the 4 work packages arranged around the two major aims related to LM biosynthesis as well as function and role as targets of LMs in A. fumigatus - innate immune cell interactions. A. fu-migatus conidia induce LT formation. At the same time virulence determinants such as gliotoxin modulate the out-come of overall LM profiles with distinct sets of SPMs and PGs/LTs. Abbreviations: afEV, antifungal extracellular vesi-cle; glio, gliotoxin; MAPK, mitogen-activated protein kinase; PGs/LTs, prostaglandins/leukotrienes; ROS, reactive oxy-gen species; SPMs, specialized pro-resolving mediators.

Principal Investigator
Prof. Dr. Oliver Werz
Prof. Dr. Oliver Werz

Department of Pharmaceutical and Medicinal Chemistry

Friedrich Schiller University Jena

Author Year Title Journal Links
Schimanski J, Gresnigt MS, Brunner E, Werz O, Hube B, Garscha U 2024 Hyphal-associated protein expression is crucial for Candida albicans-induced eicosanoid biosynthesis in immune cells. Eur J Immunol:e2350743 PubMed
Grosse M, Günther K,  Jordan PM, Roman D, Werz O, Beemelmanns C 2022 Synthesis of functionalized δ-hydroxy-β-keto esters andevaluation of their anti-inflammatory properties. ChemBioChem e202200073 PubMed
Garcia-Moreno M, Jordan PM, Günther K, Dau T, Fritzsch C, Vermes M, Schoppa A, Ignatius A, Wildemann B, Werz O, Löffler B, Tuchscherr L 2022 Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms. Front. Microbiol. 937466 PubMed