Microbe-associated immunomodulatory metabolites: Influence on T cell fate and function

• Meta-MAMPs are microbial-derived metabolites that influence immune responses by affecting specific cellular processes.
• Meta-MAMPs can modulate T cell fate by targeting intracellular metabolic pathways.
• Rapamycin and soraphen A represent two prominent examples of meta-MAMPs
• The importance of studying meta-MAMPs and their impact in cell metabolism for potential use as immunomodulatory therapies.

During the past two decades, a growing interest surrounding the interaction between microbe-associated molecular patterns (MAMPs) and pattern recognition receptors has occurred. This attention is now driven alongside bacterial-derived metabolites, which impact immune cell differentiation and function. Hence, this review introduces the term meta-MAMP as a means to classify the microbial derived-metabolites, which influence the immune response by affecting specific cellular processes. We discuss two prominent examples of meta-MAMPs: the first, rapamycin (isolated from Streptomyces), was discovered in the 1970s and since then has been thoroughly studied. The second, soraphen A (isolated from Myxobacteria), was discovered in the early 1990s but only recently identified as a promising immunomodulator. Both meta-MAMPs are similar in their remarkable capacity to modulate T cell fate by targeting key metabolic pathways triggered upon T cell activation. In this context, we highlight the progress made in the field of immunometabolism and the possibility of modulating metabolic pathways such as cellular fatty acid metabolism as a strategy for immunomodulation. We focus on the use of microbial metabolites as auspicious agents for T cell fate modulation.