Harnessing Innate Trained Immunity To Eliminate Persistent, Drug-Resistant And Subsequent Infections

An increasing body of literature demonstrates that different microbial products can induce memory-like trained immunity, reprogramming innate immune cells to provide significantly better protection against pathogens. Experimental and clinical trials have elucidated that innate immune cells, in particular, monocytes, macrophages, and natural killer cells, can exhibit prolonged and enhanced memory-like characteristics, following an external stimulus. Not only can this functional reprogramming provide rapid protection against the initial pathogen, but it can also enhance protective responses against a variety of invading organisms, without prior exposure, explaining the non-specific protection elicited from tuberculosis and measles vaccines. This innate ‘Trained Immunity’ results from epigenetic reprogramming, leading to enhanced cytokine production, cellular activation as well as changes in the host metabolic state, from oxidative phosphorylation toward aerobic glycolysis. In addition to effects on innate cell subsets, studies centered on mechanisms of metabolic reprogramming of hematopoietic stem cells also provide new insights on mechanisms underlying the trained innate immune memory. Induction and modulation of trained immunity is a novel area in the field of infectious diseases. It provides a potential platform for successful immunotherapy design to treat and eliminate persistent, drug-resistant, and latent infections where current treatments are ineffective or fail. Identification of microbial and endogenous ligands that could promote trained immunity and defining specific mechanisms of trained immunity may provide tools for the development of novel vaccines and will aid in the discovery of new therapeutic targets and approaches for infectious diseases.

This Research Topic encourages original research articles, brief research reports, perspective, opinion articles and reviews laying foundation into the development of immunotherapy used to prevent and treat infectious diseases.

Topics of interest include, but are not limited to:
• Infectious and non-infectious microbial factors as potent inducers of trained innate immunity
• Epigenome-wide and proteomic screenings to identify host responses contributing to the development of trained immunity and tolerance to microbial infections
• Characterizing the cellular signaling mechanisms of trained immunity
• Understanding the biochemical mechanisms/metabolic profiling of innate immune cells leading to clearance of microbial infections
• Designing novel prophylactic and therapeutic strategies against infectious diseases based on molecular (as listed above) profiling of trained immunity
• Identification of endogenous ligands or host metabolites/metabolic signals for induction of trained immunity to prevent or treat infectious diseases
• Improving treatment outcomes for infectious diseases by combinational approaches of trained immunity “inducers” (microbial or host endogenous) with currently used chemotherapies
• Hematopoietic stem cells: trained immunity and infection
• Trained immunity enhancing protection against infections in cancer patients
• Induction of innate protection by infectious agents reducing tumor formation
• Reprogramming innate immunity to prevent opportunistic bacterial infections in HIV patients/models
• Influence of the gut microbiome in the development of trained immunity and tolerance to infectious diseases