Descripción del proyecto
Los lipopolisacáridos de la microbiota intestinal: un enigma inmunitario
Los lipopolisacáridos (LPS) son glucolípidos presentes en la membrana externa de las bacterias gramnegativas y pueden desencadenar respuestas inflamatorias. Los LPS también se encuentran en las membranas de microbios intestinales inofensivos y beneficiosos, en los que están paradójicamente «inactivos» desde el punto de vista inmunitario. El proyecto DEBUGGING-LPS, financiado con fondos europeos, tiene por objeto abordar esta cuestión no resuelta sobre la capacidad inmunógena de los LPS. La hipótesis de trabajo es que la química de los LPS de estas bacterias intestinales no tiene precedentes y se traduce como una señal de inmunotolerancia en el intestino. Los resultados del proyecto aportarán información fundamental sobre la inmunidad local y sistémica y ayudarán a analizar minuciosamente la relación de tipo comensal y mutualista de la microbiota intestinal con el hospedador. Además, los conocimientos adquiridos abrirán nuevas oportunidades para diseñar tratamientos novedosos contra los trastornos inmunitarios.
Objetivo
Gut Microbiota is a key actor for human health, driving many physiological and pathological processes, including immune system development and modulation. How this massive population of microorganisms, most of which are bacteria, establishes commensal, mutualistic or pathogenic interactions with the human host despite the vigilance of the immune system, is still obscure and requires an in-depth study. The story gets more intricate considering that gut is home for a myriad of Gram-negative bacteria whose outer membrane main constituent is the lipopolysaccharide (LPS). Due to its chemical structure, LPS is considered a potent elicitor of immune inflammatory reactions in mammals, being usually associated to perilous bacteria and detrimental outcomes for human health. Nevertheless, LPS also decorates the membrane of harmless and beneficial Gram-negatives of gut microbiota. How LPS is tolerated and remains (apparently) silent in the gut is a major unsolved question representing a frontier in our understanding of innate immunity.
DEBUGGING-LPS project will contribute to answer this question, starting from the assumption that the chemistry of LPS is the real message taken from human host of the bacterial interaction, either beneficial or harmful. Strategically based on my expertise in organic chemistry, and integrating synthetic chemistry and cellular immunology studies, DEBUGGING-LPS will decrypt the 'chemical language' spoken by LPS in the gut. This project will deliver a clear picture of the chemistry at the basis of the difference between 'good' and 'bad' LPS, providing tools for the exploitation of the acquired knowledge to create novel therapeutics for resolving/mitigating immune disorders. DEBUGGING-LPS has been conceived to go beyond the state-of-the-art, breaking the dogma of LPS as an enemy, leaving space for a new vision of this glycomolecule: i.e. no longer as a toxic bacterial product rather as an immune signal vital for the proper functioning of our body.
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-AG - HORIZON Action Grant Budget-BasedInstitución de acogida
80138 Napoli
Italia