Immunobiology

Our lab studies dendritic cells (DCs) and macrophages, key immune sentinels that regulate immunity, inflammation, and tolerance. As gatekeepers of the immune system, these cells not only defend against pathogens but also maintain balance to prevent self-damage. Because of their unique ability to shape immune responses, they are promising targets for new therapies against infectious, autoimmune, cardiovascular diseases (CVD), and cancer. We also explore the dialogue between the microbiota and the immune system. Our research is integrated within the “Novel Mechanisms of Atherosclerosis” program at the CNIC. Our main research lines are:

  1. Molecular pathways controlling trained immunity (TI) in macrophages and its role in atherosclerosis. TI is an emerging concept that describes the long-term hyperactivation of innate immune cells following certain stimuli. Unlike classical adaptive memory, TI involves epigenetic reprogramming of myeloid cells that amplifies their response to secondary challenges. This heightened state can be beneficial, as it enhances protection against invading pathogens (Brandi et al., Cell Reports 2020; del Fresno et al., Front. Immunol. 2021). However, when unresolved, sustained overactivation contributes to chronic vascular inflammation and progression of atherosclerosis (AT). Notably, microbiota translocation can trigger TI and promote inflammation (Robles-Vera et al. Immunity. 2025). Our group is investigating the molecular regulators of TI and their specific contribution to vascular pathology.
  2. Immunometabolic mechanisms regulating DC and macrophage function. Immune cell activity is intimately linked to their metabolic state. We are studying how sensing of microbial and damage-associated signals reshapes the metabolism of DCs and macrophages, and how these changes determine their capacity to either resolve or perpetuate inflammation. Our findings highlight mitochondrial metabolism and dynamics as critical checkpoints in this process (Hernández-García et al., Cell Mol Immunol. 2022; Wculek et al., Immunity 2023). By targeting these pathways, we aim to design new immunotherapy strategies that can modulate immune cell function in cardiovascular and other immune-mediated diseases (Cueto et al., JITC 2021; Heras-Murillo et al., Nat. Commun. 2025; Galán et al., Circ. Res. 2025).
  3. Gut microbiota, microbial metabolites, and atherosclerosis. Our recent studies have identified imidazole propionate (ImP) as a microbial-derived metabolite associated with active inflammatory atherosclerosis in both mouse models and human cohorts. Notably, ImP promotes atherosclerosis independently of lipid levels, suggesting a novel mechanism of disease. We have also identified the host receptor (I1R) for ImP and demonstrated that blocking this pathway prevents disease progression (Mastrangelo et al., Nature 2025). These discoveries open new possibilities for early diagnosis and personalized therapeutic approaches in cardiovascular disease.

Together, these research directions aim to uncover fundamental principles of immune regulation, while translating this knowledge into innovative strategies to combat chronic inflammatory conditions such as atherosclerosis.