When pathogens invade the body, our immune system memorizes characteristic components of the invaders and forms memory cells that can respond quickly upon re-exposure. However, this recall immunity triggers a much stronger defense in some people than in others. The joint MARITH project (Mapping Recall Immunity in Human Tonsil Organoids Across Viral Histories) aims to understand the underlying mechanisms more precisely. Researchers plan to create organoids from tonsil tissue from donors. These mini-organs will be used to study how the human immune system recalls previous encounters with viruses. Current insights into immune memory are mainly based on analyses of blood samples and animal models. While these approaches have yielded important findings, they do not precisely reflect what happens on the mucosal surfaces through which many pathogens enter the body.
Because the tonsils sit at the front line of the respiratory tract, they are particularly exposed to viruses transmitted through air and droplets. They harbor B- and T-memory cells formed after prior encounters with pathogens such as SARS-CoV-2, seasonal coronaviruses, and measles/mumps viruses, and thus play a key role in recognizing newly arriving viruses. “I am very pleased about the funding for this project, because tonsils are an ideal tissue to study important aspects of the human immune response,” says Dr. Kristin Metzdorf, deputy head of the department “Innovative Organoid Research” at the HZI. “From tonsil tissue, we can grow organoids that reflect key characteristics of their natural environment and contain functional immune cell populations.” The project receives a total of 100,000 euros in funding. Partners are HZI (50,000 euros), MRC–University of Glasgow Centre for Virus Research (30,000 euros), and the Hannover Medical School (20,000 euros).
The second funded collaboration — ViReST (Mapping Viral Replication Sites in the Respiratory Tract to Predict Disease Severity and Transmission) — investigates the sites of viral replication in respiratory infections and their impact on virus transmission. The severity of symptoms in a viral respiratory infection largely depends on how deeply the viruses penetrate the airways and where they replicate. Viruses like SARS-CoV-1 or H5N1 influenza viruses primarily infect the lower airways and often cause severe disease, while seasonal coronaviruses tend to stay in the upper airways and cause milder symptoms. The location and severity of infection also influence the mucus secretions produced by the mucosa, and thus the properties of droplets formed during breathing, speaking, or coughing, which are major routes of transmission. A further transmission route is direct contact with body fluids. “The precise mechanistic links between the site of viral replication, virulence—the disease-causing potential of the viruses—and transmission have not yet been clarified,” says Dr. Julia Port, head of the research group “Laboratory of Transmission Immunology” at the HZI. “In ViReST, we want to examine whether patterns of viral replication influence virulence and to what extent zoonotic viruses may need to adapt to the upper airways after the initial spillover from animals to humans to achieve human-to-human transmission.”
ViReST is also funded with a total of 100,000 euros, of which 37,000 euros go to HZI. Other partners are MRC–University of Glasgow Centre for Virus Research (50,000 euros) and Technische Universität Braunschweig (13,000 euros) with Prof. Melanie Brinkmann, who also leads a research group at HZI. The collaboration is part of TU Braunschweig’s Ecoversity program.
