Affiliation: University Hospital Zurich, Institute of Neuropathology
Link to group website: Website
Prof. Aguzzi has devoted the past 20 years to studying the immunological and molecular basis of prion pathogenesis. Combining transgenetics with molecular and immunological techniques, he has aimed to clarify the pathogenesis of the disease, and to identify cells and molecules involved in prion neuroinvasion.
The discovery of pervasive colonization of the immune system by prions has convinced most of the world’s governments to undertake efforts to limit the exposure of humans to prions derived from farm animals. As further crucial practical consequence of Prof. Aguzzi’s discoveries, the UK government has started, in the year 1998, universal mandatory leukodepletion of donated blood units. This measure was very controversial at the time, but it has probably saved many lives, since not a single case of blood-borne transmission of Creutzfeldt-Jakob disease was recorded in recipients of UK blood after its introduction.
Prof. Aguzzi’s discovery that chronic inflammation controls the organ tropism of prion diseases has crucially contributed to clarifying how scrapie transmits horizontally within sheep flocks – a question that had been controversially discussed since the late 19th century. The realization that prion excretion necessitates inflammation of the excretory organ as a cofactor in addition to prion infection will pave the way to effective strategies for the eradication of prion diseases from small ruminants.
His work on microglia was seminal to establish that microglia is helpful, rather than detrimental, in fighting prion diseases. Using original models of conditional lineage ablation, Prof. Aguzzi has shown that the removal of microglia greatly accelerates prion disease. This discovery has a fundamental impact on therapeutic strategies against aggregation proteinopathies, and clearly indicates that the innate immunity provided by microglia is important and should be facilitated.
Finally, his work related to the histogenesis of follicular dendritic cells, which spans over a decade and has culminated in a Cell paper, has clarified how ectopic lymphoid organs can arise anywhere the body following chronic inflammatory stimuli. This discovery has profound consequences for our understanding of the factors controlling chronic inflammation and autoimmunity.