Project Details
Projekt
Tissue distribution and antiviral response of primary human dendritic cells
Applicant
Dr. Anna Eichinger
Subject Area
Immunology
Term
from 2020 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 442666094
Dendritic cells (DCs) are immune cells at the interface of the innate and adaptive immune system working as sentries. They are the most potent antigen-presenting cells priming naïve T cells. Moreover, they can trigger a variety of other reactions via second messengers. For example, they can induce an antiviral state in cells surrounding infected cells or summon cells of the innate immune system. Thus, they are at the starting point of a variety of immune system functions, giving them an important role in the fight against infections and cancer.The constant work of the immune system is mirrored in its interactions with cytomegalovirus (CMV). By adulthood CMV has infected more than half of the population. After the primary infection, CMV stays in the body in a latent state with recurring flares of viral replication. Thus CMV constantly challenges the immune system and in immunocompromised individuals, e.g. fetuses and patients after kidney transplantation, CMV can outwit the immune surveillance and lead to severe injury and even death.Most of our knowledge about DCs stem from studies in mice and from the peripheral blood of humans. Information on DC in the healthy human tissue is limited. The Reizis Lab, together with cooperation partners, has started to deepen the knowledge on tissue DCs in the healthy state, as they were able to analyze different human tissues from research-consented human organ donors, using tissues that were not going into transplant (Granot et al. 2017).The overall goal of my project in the Reizis Lab is to characterize the diversity, tissue specificity and functionality of DC populations on the whole-body scale, with particular emphasis on their response to CMV. We plan to combine the unique source of DC populations isolated from the tissues of healthy individuals (CMV-positive and -negative) with high-dimensional analysis tools and functional assays. To this end, we propose two subprojects: In the first one, we will analyze DC subtypes across tissues. With the help of mass cytometry, we will assess a variety of surface activation markers and signaling molecules, taking the influence of tissue latency of CMV in account. Additionally, we will describe the microenvironment and tissue niche of DCs using CODEX, a new fluorescence imaging technique. In the second subproject, we will measure the response of DCs isolated from different tissues from CMV-seropositive and CMV-seronegative individuals to CMV and CMV-infected cells in cell culture.Through these experiments we hope to understand tissue-specific features of the different DC subsets and how they interact with latent CMV infection. In the future, these results might play role in vaccine strategies and novel treatment options.
DFG Programme
Research Fellowships
International Connection
USA
