Descripción del proyecto
Aportar datos sobre el rompecabezas inmunitario
Se tienen pocos conocimientos sobre los procesos que facilitan la eliminación eficaz de los autoantígenos de las células apoptóticas y necróticas, que permite al sistema inmunitario responder eficazmente a los microorganismos patógenos invasores. La falta de técnicas adecuadas ha dificultado la identificación y el seguimiento de subconjuntos específicos de fagocitos responsables de la eliminación simultánea de células muertas y microorganismos patógenos en un organismo vivo. Para hacer frente a estas limitaciones, en el proyecto SOS, financiado por el Consejo Europeo de Investigación, se pretende desarrollar herramientas innovadoras que aporten datos sobre los intrincados mecanismos que intervienen en la eliminación de células muertas y microorganismos patógenos, sobre todo cuando hay inflamación. El objetivo del proyecto es mejorar la comprensión de las causas subyacentes de las enfermedades autoinmunitarias e infecciosas y fomentar el desarrollo de enfoques terapéuticos innovadores.
Objetivo
During inflammation and infection, we are simultaneously confronted with both self and non-self in form of dying cells and microbes, respectively. Mechanisms that facilitate the non-immunogenic clearance of self-antigens derived from apoptotic and necrotic cells and that, in parallel, allow the initiation of an immune response against invading pathogens are incompletely understood.
Recent data from our laboratory show that the immune system actively sorts apoptotic cells (ACs) and bacteria into distinct subspecies of macrophages and dendritic cells thereby enabling a segregated processing of self and non-self as well as a differential immune response against these two entities. Incorrect sorting and aberrant uptake of AC-derived self-antigens by pro-inflammatory and antigen-presenting dendritic cells, however, results in the break of self-tolerance and autoimmunity.
Due to technical limitations, the identification and fate-mapping of specific phagocyte subsets that mediate the simultaneous clearance of dying cells and pathogens in vivo has remained largely elusive. We thus plan to develop novel tools that are based on cutting-edge technologies to comprehensively elucidate the sorting of dying cells and pathogens under inflammatory conditions in vivo. We plan to generate TAT-Cre transgenic mice and bacteria that will be used in conjunction with R26-eYFP reporter animals to permanently track phagocytes after ingestion of endogenously accumulated dying cells and pathogens, respectively. These approaches will enable us to characterize the involved phagocytes, study molecular mechanisms underlying the differential processing of self and non-self and follow the phagocyte’s migratory behaviour and its subsequent differentiation. The obtained data will not only provide insights into the pathogenesis of autoimmune and infectious diseases, but will also foster the development of novel therapeutic strategies for the treatment of such disorders.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
91054 Erlangen
Alemania