Davide Pisu, PhD

Research Interests

• Host–pathogen interactions during early Mycobacterium tuberculosis infection, including determinants of bacterial permissiveness and control.
• Lung macrophage heterogeneity, ontogeny, and functional state transitions in health, tuberculosis, and HIV–TB co-infection.
• Granuloma formation and evolution, with emphasis on immune cell organization and function within infected lung tissue.
• Macrophage–T cell interactions and their role in shaping local and systemic immune responses during mycobacterial infection.
• Transcriptional, epigenetic, and chromatin-level regulation of immune responses to intracellular pathogens.
• Use of non-human primate and murine models, combined with single-cell and multimodal genomic approaches, to study infectious disease pathogenesis.
   

Research Programs
 

Macrophage heterogeneity in tuberculosis infection outcomes

Tuberculosis is initiated and sustained within lung macrophages, yet these cells are highly heterogeneous in origin, function, and permissiveness to Mycobacterium tuberculosis. Our research focuses on how distinct alveolar and recruited macrophage subsets shape early infection outcomes, including bacterial survival, immune activation, and progression toward protective or permissive disease states. We investigate how macrophage ontogeny, activation state, and transcriptional and epigenetic programs determine differential control of M. tuberculosis during the earliest stages of infection, before adaptive immunity is fully established.

HIV–TB co-infection and macrophage dysfunction in the lung

HIV infection dramatically increases the risk of active tuberculosis, even in individuals receiving antiretroviral therapy. A major focus of our work is to define how HIV alters macrophage biology in the lung and compromises early control of M. tuberculosis. We study how HIV-driven immune dysregulation affects alveolar macrophage function, macrophage–T cell interactions, and inflammatory balance during TB infection, with particular emphasis on mechanisms that destabilize granuloma integrity and promote disease progression in co-infected hosts.

Granuloma formation and immune cell interactions

Granulomas represent the central pathological and immunological structures of tuberculosis, yet the cellular interactions that govern their formation and function remain poorly defined. Our research examines how macrophages organize, maintain, and remodel granulomas, and how their interactions with T cells and other immune populations influence local immune responses and bacterial control. By studying granulomas at early and intermediate stages of infection, we aim to define how immune cell composition and spatial organization determine protective versus pathogenic outcomes.

Host–pathogen determinants of tuberculosis pathogenesis in animal models

We use complementary murine and non-human primate models of tuberculosis to identify host and bacterial factors that govern M. tuberculosis pathogenesis in vivo. These models provide access to early infection events and lung tissue compartments that are not readily accessible in humans. By integrating in vivo infection models with single-cell and multimodal genomic approaches, we investigate bacterial gene requirements, host immune states, and their intersection within defined macrophage populations to understand mechanisms of TB pathogenesis and persistence.