Archaeome - immune system interactions

• Applicant: Professor Dr. Holger Heine
• Subject Area: Immunology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 557305332

The human body is populated by communities of bacteria, archaea, viruses/phages and small eukaryotes, the so-called microbiome. Numerous studies have demonstrated a fundamental role of the human microbiome in health and disease. However, most microbiome studies focus exclusively on the bacterial microbiome and therefore largely overlook the other integral microbial components - particularly archaea. Archaea differ substantially from bacteria in cell structure, metabolism, and molecular machinery. Methanogenic archaea in the gastrorespiratory tract utilize bacterial fermentation products, creating favorable thermodynamic conditions for optimal microbiome function in the host. Although more than 1000 genomes of intestinal archaea are currently available, the few existing archaeal isolates from the human microbiome are poorly characterized, and their interaction with the host remains a mystery. However, the interaction of microorganisms with the host plays an essential role in the development, formation, and actual function of the immune system. Methanosphaera species in particular could play a major role in this regard and minimize asthma risks. Our recent work has shown that methanogenic archaea are recognized by the innate immune system via their RNA through TLR8/7, and the level of immune activation is species-dependent. In this case, for the RNA to be immunogenic, the archaeal RNA must enter the endosomal compartment of immune cells by phagocytosis. This process of phagocytosis, and in particular the cell wall-associated archaeal triggers for phagocytosis, are completely unexplained, as is the processing of the ingested archaea in the phagolysosomes until the release and presentation of the archaeal RNA to TLR8/7. We hypothesize that differential immune activation by archaea could be due to differential uptake and/or degradation within the phagolysosome, both of which result in different amounts of RNA that are then available for activation of TLR8/7. In our project, we will analyze how different archaea from the human microbiome differ in terms of their cell wall architecture and composition, which receptors are responsible for archaeal uptake/phagocytosis, and which archaeal cell wall components carry the responsible binding domains. In addition, we are investigating how Archaea are processed after phagocytosis to allow presentation of their RNA to TLR8/7, and finally, whether growth of Archaea under syntrophic conditions alters their immunogenic activity.

• DFG Programme: Research Grants
• International Connection: Austria
• Partner Organisation: Fonds zur Förderung der wissenschaftlichen Forschung (FWF)
• Cooperation Partner: Professorin Dr. Christine Moissl-Eichinger