Activation of nuclear receptors correlates with tuberculosis severity and is a target for host-directed therapy

Introduction: The immune response to Mycobacterium tuberculosis is accompanied by metabolic adaptations that fuel host immunity, but that are exploited by the pathogen to ensure persistence and growth. Activation of nuclear receptors, such as liver-X-receptors (LXR), orchestrate macrophage immunometabolic adaptations to infection and globally associate with tuberculosis (TB) protection. Methods: We interrogated available transcriptomic datasets of whole blood from TB patients or M. tuberculos...

Infection with hypervirulent Mycobacterium tuberculosis triggers emergency myelopoiesis but not trained immunity

Introduction: During infection, bone marrow (BM) hematopoiesis is reprogrammed toward myeloid cell production, a mechanism named emergency myelopoiesis. In addition to replenishing myeloid cells, emergency myelopoiesis has been linked to trained immunity, a process that allows enhanced innate immune responses to secondary challenges. Although hematopoietic alterations during tuberculosis (TB) have been described and Mycobacterium tuberculosis may colonize the BM, studies using the mouse model...

Decellularised Cartilage-Based Hydrogels Functionalised With Chondroitin Sulphate and Quercetin: The Impact on Chondrogenesis

Tissue engineering and regenerative medicine approaches are being actively developed for degenerative disorders, including osteoarthritis (OA). Decellularized matrix (dECM) is a promising biomaterial; however, glycosaminoglycan (GAG) loss during decellularization limits its chondrogenic potential. In this study, we aimed to overcome this by developing a dECM hydrogel originating from cartilage, functionalized with the GAG chondroitin sulphate (CS), to replenish those originally depleted and i...

Genetically Diverse Mycobacterium tuberculosis Isolates Manipulate Inflammasome and Interleukin 1β Secretion Independently of Macrophage Metabolic Rewiring

The diversity of Mycobacterium tuberculosis impacts the outcome of tuberculosis. We previously showed that M. tuberculosis isolates obtained from patients with severe disease induced low inflammasome activation and interleukin 1β (IL-1β) production by infected macrophages. Here we questioned whether this differential modulation of macrophages by M. tuberculosis isolates depended on distinct metabolic reprogramming. We found that the macrophage metabolic landscape was similar regardless of the...