Group | Tuberculosis Immunology

Human immune responses are in many instances efficient enough to prevent infection by Mycobacterium tuberculosis (Mtb). Mtb virulence relies notably on its capacity to escape the bactericidal functions of macrophages despite potentiation by NK and T cell-derived cytokines. To support the development of host-directed therapies and new vaccines against TB, we aim to understand the interplays between host-pathogen genetic traits, co-infections and environmental factors that hamper immune functions and pave the way for active TB disease.

In vitro, ex vivo and in clinico evidence are pointing towards substantial phenotypic heterogeneity across Mtb populations that can be linked to virulence traits such persistence, tolerance, reactivation and transmission. Using clinical Mtb isolates and cellular models of infection, encompassing macrophage and in vitro granuloma, we aim to dissect the contribution of individual immune cell types and their products that would favor or prevent Mtb physiological variation at the population level and influence aforementioned Mtb virulence traits.

Non-sputum based biomarkers diagnostic tools are required to overcome the paucibacillary nature and extra-pulmonary propensity of TB/HIV co-infection and childhood TB. We previously demonstrated unprecedented accuracy of an immunodiagnosis approach measuring phenotypic markers of Mtb-specific T cells by flow cytometry. We are aiming to refine and develop this assay towards a point-of-care test.