Novel In Vivo Imaging Techniques to Explore Microbiome-Immune System Interactions

Jeya Chelliah B.Vsc Ph.D.

Recent advancements in microbiome research have underscored the profound impact of microbial communities on host physiology, particularly through their interactions with the immune system. To explore these interactions in unprecedented detail, we propose a novel experimental approach utilizing advanced in vivo imaging techniques combined with genetic and metabolic profiling. This method involves the use of multi-photon intravital microscopy to visualize real-time interactions between specific microbial taxa and immune cells within their natural tissue environments. Coupled with CRISPR-Cas9 mediated gene editing, we can selectively label microbial species and immune cell subtypes with fluorescent markers, enabling precise tracking and analysis of their dynamic interactions.

Understanding the intricate crosstalk between the microbiome and the immune system is pivotal for uncovering new therapeutic avenues for various diseases. For instance, in cancer treatment, the microbiome’s modulation of immune checkpoints could enhance the efficacy of immunotherapies. In type 1 diabetes, deciphering how microbial metabolites influence regulatory T cells might reveal strategies to prevent or reverse autoimmune attacks on pancreatic islets. Similarly, for autoimmune diseases, the ability to regulate immune responses through microbiome manipulation could lead to targeted therapies that restore immune homeostasis.

An illustrative example of this innovative approach is the investigation of how specific microbiome-derived metabolites affect the activity of regulatory T cells (Tregs). By utilizing our proposed imaging technique, we can observe how these metabolites enhance Treg function while simultaneously downregulating effector T cells. This dual modulation can potentially be harnessed to dampen autoimmunity and enhance anti-tumor immunity, providing a twofold therapeutic benefit. Thus, this novel approach not only deepens our understanding of microbiome-immune system interactions but also paves the way for innovative treatments for cancer, type 1 diabetes, and autoimmune diseases.

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