Principal Investigator (PI)
The Foundation is providing £213,180 in support.
Ignacio Cardona, Celia Vived
- Unique animal facilities and personnel: Humanized immune system mice are severely immunosuppressed and require proper housing facilities, trained personnel and strict policies. Proper animal handling will be essential to achieve project objectives.
- Access to PET/CT installed by UC3M in GHM in vivo facilities.
- Skills and experience for the quality control and stratification of the animal and for the longitudinal characterization of immune system responses after therapeutic interventions.
- Scientific support.
The outcome of Mycobacterium tuberculosis (Mtb) infection is the result of a multifaceted interplay of both innate and adaptive responses. The complexity of host-pathogen interaction has necessitated the development of multiple animal models traditionally designed for the active form of the disease and mainly focused on reproducibility and homogeneity.
These models have been useful to understand the evolution of the disease as well as the effectiveness of different therapeutic approaches to eliminate the infective agent. However, none of them reflect the complex pathology characteristics of human disease and the different susceptibility of the bacteria populations present in the diverse regions of the lesions.
We propose the use of a Mtb CD34+ Humanized Mice as a meaningful tool to develop an integrated and translational model for TB disease progression. The implementation of an in vivo model covering human immunological pathways will enhance the knowledge of human defences acting during Mtb infection and the development of innovative interventions bending host-pathogen interaction in favour of the host to complement the traditional pathogen-directed therapies.
A translational TB model based on mice reconstituted with human immune cells offer a unique opportunity to comprehensively understand host-pathogen interactions and to evaluate new therapeutic strategies focused on host-directed therapy (HDT), help cure drug-resistant disease or limit immunopathology.