The nonspecific protection provided by the innate immune system can be enhanced through training with stimuli, a phenomenon called ‘trained immunity’. However, it remains unknown if distinct training programs with various functional outcomes can be induced. Here, we show that two training agents, flunisolide and myricetin, distinctively train and modulate the immune response against in vivo Listeria monocytogenes infection. Training with either agent led to significant reduction in pathogen burden but differed in the resulting immune functions. Training with myricetin led to the expansion of myeloid progenitor lineages, rapid cell recruitment, and enhanced phagocytosis. In contrast, training with flunisolide led to expansion of stem cell and multipotent progenitor populations, increase in antigen processing, and faster T cell expansion. We provide preliminary evidence that this divergent training outcomes may arise from agent-specific modulation of transcription factors. This study importantly shows that training can be directed at both the innate response and the onset of the adaptive response, highlighting the potential of modulating distinct training programs to influence protective immune responses.
Introduction Vaccination is the most common method used to control infection caused by Mycoplasma gallisepticum in chickens. However, concurrent immunosuppression may compromise vaccine efficacy. Methods This study investigated the effect of immunosuppression induced by either ch…
Introduction The updated SOFA-2 score excludes the immune system due to specificity concerns, creating a conceptual gap given that sepsis is defined by a dysregulated host response. We hypothesized that augmenting SOFA-2 with widely available immune markers—white blood cell count…
Vaccination relies on innate and adaptive responses initiated at the injection site followed by activation in draining lymph nodes. However, high-plex, spatially resolved maps that couple injection site signals with transcriptomic programs in draining lymph nodes over time are st…
Immune checkpoint blockade has transformed cancer therapy, yet many tumors remain intrinsically resistant or acquire resistance after initial response. Increasing evidence indicates that this failure is not determined solely by PD-1, PD-L1, CTLA-4, or T-cell exhaustion, but also…
Prostate cancer is a typical age-associated malignancy, and increasing evidence suggests that age-related immune alterations play an important role in its initiation, progression, and therapeutic response. Immunosenescence, characterized by impaired immune surveillance, reduced e…
Persistent antigenic stimulation leads to the dysfunction of CD8 + cytotoxic T cells. These “exhausted” T EX cells exhibit reduced proliferative capacity, impaired effector function, and increased expression of co-inhibitory receptors. Chronic antigen receptor stimulation induces…