Iris

Our immune system is in balance with the body’s own bacterial environment. These so-called commensal bacteria are also essential for the correct functioning of our skin and integrity. Under certain circumstances commensal bacteria can develop resistance against antibiotics and become pathogenic organisms, causing fulminant and almost uncontrollable infections. Therefore, it is of central importance to identify the so far unknown interactions between microorganisms immune system orchestrating tolerance and host defense.

Based on the collected data we were able to encrypt and modulate the immune response against pathogenic and commensal bacteria.

Through the IRIS project, the network partners achieved a comprehensive and unprecedented characterization of more than 100 clinical and commensal isolates of Staphylococcus epidermidis using state-of-the-art molecular and immunological methods such as RNAseq, next-generation sequencing, qPCR, microbiome profiling, gnotobiotic mouse models, co-culture systems, and multiparameter flow cytometry. These efforts revealed an unexpectedly high genetic diversity across isolates, including substantial variation in virulence and resistance genes. The team generated a microbiome atlas in animal models, established strain-specific qPCR assays, and mapped the complex interactions between skin microbes and the host immune system. One of the most significant breakthroughs was the identification of the immune checkpoint CD86 on DC2 dendritic cells as a central regulator of memory T-cell activation against S. epidermidis. In parallel, the researchers demonstrated that even harmless, commensal strains can trigger systemic immunosuppression by inducing IFN-γ–dependent nitric oxide production, which selectively impairs CD8⁺ T-cell function. These findings fundamentally reshape our understanding of how skin bacteria influence immune tolerance and activation.

Beyond scientific insights, IRIS delivered a suite of tangible tools and translational innovations. The consortium developed new diagnostic and experimental platforms—including co-culture systems to study dendritic cell–T-cell interactions, gnotobiotic mouse models for microbe–host studies, and multiparameter flow cytometry pipelines for detailed immune profiling—that can directly inform future therapeutic strategies. The project produced several patent applications (such as “Artificial Immune Receptors”) and high-impact publications in journals including Cancer Discovery, The Journal of Clinical Investigation, and Frontiers in Microbiology. By integrating microbial genomics with immunological and functional datasets through AI-supported analytical frameworks, IRIS established a foundation for novel immunotherapeutic approaches against multidrug-resistant pathogens. At the same time, it strengthened Bavaria’s position as a leading center for innovation, supported early-career scientists, and increased public visibility of immunology research. Together, these outcomes make IRIS a model for interdisciplinary, digitally integrated, and clinically relevant infection research with long-lasting impact.