HSPCs are able to respond to stress, such as severe infection, systemic inflammation, or iatrogenic myeloablation, by increasing their proliferation rate and hematopoiesis ( Trumpp et al., 2010, Zhao and Baltimore, 2015). Hematopoiesis is a hierarchical system, in which hematopoietic stem and progenitor cells (HSPCs) are responsible for its maintenance via their differentiation into progressively committed progenitors and mature cells ( Trumpp et al., 2010).
We have, thus, hypothesized that the adaptive processes induced by trained immunity involve alterations to progenitors of the hematopoietic system, a concept that has not been addressed yet. However, the long-term effects (up to months) of trained immunity on circulating monocytes are puzzling, as these cells have a relatively short lifespan in the circulation. Transcriptomic and metabolomic analysis have implicated metabolic pathways, especially glucose metabolism, in the adaptation of monocytes and macrophages in the context of innate immune memory ( Arts et al., 2016a, Arts et al., 2016b, Cheng et al., 2014, Netea et al., 2016). Pathogen-associated molecular patterns or cytokines induce a complex immunometabolic program in monocytes and macrophages, enabling a robust cellular response to re-stimulation, especially with regard to cytokine production ( Arts et al., 2016a, Netea et al., 2016, Quintin et al., 2012). This process involves changes in cell transcription and is designated “trained immunity” ( Goodridge et al., 2016, Jensen et al., 2015, Netea and van Crevel, 2014, Netea et al., 2016, Quintin et al., 2012). Recent studies have shown that certain microbial challenges or vaccines promote a heightened response of myeloid cell populations to a subsequent infection with the same or even different pathogens.
Therefore, modulation of myeloid progenitors in the bone marrow is an integral component of trained immunity, which to date, was considered to involve functional changes of mature myeloid cells in the periphery. The trained-immunity-related increase in myelopoiesis resulted in a beneficial response to secondary LPS challenge and protection from chemotherapy-induced myelosuppression in mice. Administration of β-glucan (prototypical trained-immunity-inducing agonist) to mice induced expansion of progenitors of the myeloid lineage, which was associated with elevated signaling by innate immune mediators, such as IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF), and with adaptations in glucose metabolism and cholesterol biosynthesis. We thus hypothesized that trained immunity acts via modulation of hematopoietic stem and progenitor cells (HSPCs). Note: Complete this step only if you are going to simulate the model in accelerated mode.Trained innate immunity fosters a sustained favorable response of myeloid cells to a secondary challenge, despite their short lifespan in circulation.
Generate the rtwmakecfg.m file if the required source and header files for the S-functions are not in the same directory as the S-functions, and you want to add these dependencies in the makefile produced during code generation.
Generating an rtwmakecfg.m File for Code GenerationĪfter the TLC block file is created, the function legacy_code() can be called again with the first input set to 'rtwmakecfg_generate' in order to generate an rtwmakecfg.m file to support code generation through Simulink® Coder™.