Trained immunity, a de facto innate immune memory characterized by enhanced responsiveness to future challenges, is underpinned by epigenetic and metabolic rewiring (1). In contrast to adaptive immune memory, Trained Immunity offers a broad-spectrum enhancement of the immune response, which is not limited to specific pathogens (2). Our work previously showed that Trained Immunity can be used to reverse immune suppression (endotoxic tolerance) in sepsis patients (3). There is now a push towards the development of Trained Immunity vaccines that provide short-term non-specific protection against antimicrobial resistant pathogens (4). In this presentation, I will discuss recent work on trained immunity, including the role of a novel histone modification, lactylation of histone H3 at lysine residue 18(H3K18la) (1), and RNA Adenosine-to-Inosine modification. Through funding from the JPIAMR - Joint Programming Initiative on Antimicrobial Resistance (2025-28), I am part of an international team that is exploring how to harness the properties of Trained Immunity to protect against antimicrobial resistant fungal pathogens. This research has implications for immunocompromised patients, such as those undergoing chemotherapy.
(1) Ziogas et al., Cell (2025)
(2) Divangahi et al., Nature Immunology (2021)
(3) Novakovic et al., Cell (2016)
(4) Yan et al., Science Translational Medicine (2023)