Project 01

Adrenal susceptibility to viral and bacterial infection

• Principial Investigators:
  • TUD: Stefan. R. Bornstein & Waldemar Kanczkoski
  • UZH: Felix Beuschlein & Zsuzanna Varga 
• Students:
  • TUD: Marleen Hohnvehlmann (1st year-PhD student), Agnés Wlodarczyk (affiliated 3rd year-PhD student)

  • UZH: Alexander Kirschfink (1st year-PhD student), Hüseyin Cihan (2nd year-PhD student)

Background: During systemic microbial infections, rapid secretion of glucocorticoids from the adrenal gland is crucial for the survival of the host. Patients with bacterial and viral sepsis often develop adrenal gland insufficiency (AI), which can either be a result of impaired function of the hypothalamus and pituitary or be a direct consequence of pathogen-mediated damage to adrenocortical cells. An increasing number of studies has demonstrated that various bacterial species can be identified in the human adrenal gland at autopsies.Whether these infections might cause AI or damage such as in the case of fulminant N. meningitis infection, which is characterized by adrenal haemorrhages (Waterhouse-Friderichsen syndrome), cellular necrosis, and tissue inflammation, remains unexplored. Recently, our groups in Dresden and Zürich found compelling evidence that human adrenocortical cells are also a prominent target of viruses including SARS-CoV-2. We now aim to characterize the bacterial tropism in the adrenal gland during sepsis and to analyse whether microbial infections might directly contribute to the functional impairment of human adrenocortical cells.

Aims: 1) Transcriptomic, proteomic and functional characterization of factors involved in 
adrenocortical cell susceptibility to SARS-CoV-2 infection and in cellular damage including, 
inflammation, oxidative stress, cell death, and functional impairment.
2) Microbiome and histopathological analysis of adrenal gland from patients with sepsis and characterization of direct pathogen-adrenocortical cell interactions in in vitro infection models. 

Added value through the collaboration between Dresden & Zurich: The Kanczkowski  group has strong expertise in the regulation of adrenal gland microenvironment in infection and sepsis. The Bornstein group has in-depth expertise in intercellular crosstalk in the endocrine system, with particular focus on the adrenal gland. Both groups are closely collaborating and have thoroughly characterized adrenal gland function/dysfunction in several experimental mouse models of sepsis and gained expertise in the transcriptomic analysis of septic  adrenal glands. Beuschlein’s group has strong expertise in clinical and molecular characterization  of various adrenal gland disorders, including hyperaldosteronism and hypercortisolism. The Varga group has significant expertise in the pathological analysis of organ damage (including  after infection) as well as possesses a well-characterized collection of FFPE adrenal gland 
tissues of patients that died due to bacterial and viral sepsis.

Synergies: We will continue our established collaboration with project 2 on the role of regulated necrosis and immune-metabolism in sepsis-induced adrenocortical cell dysfunction. Furthermore, we will interact and expand our research with projects 3, 5, 6, 8 that will use different in vivo mouse infection models.