This chapter starts with by exploring the intersection of nutrition and immunity, at the example of the nuclear receptor VDR, to illustrate how adequate nutrient levels influence immune function. The innate immune system, which is central for early responses to pathogens and non-microbial danger signals, involves key cellular players such as monocytes, dendritic cells, macrophages, and neutrophils. Among these, macrophages and neutrophils are particularly crucial for phagocytosis, which is the ingestion and subsequent destruction of extracellular substrates, including microbes. This process begins with the recognition of pathogen-associated molecular patterns (PAMPs) by pattern-recognition receptors (PRRs), initiating a signaling cascade that activates the inflammasome and triggers cytokine secretion. Similarly, damage-associated molecular patterns (DAMPs) can provoke analogous inflammatory responses. Nutritional factors can modulate these inflammatory processes. For example, inadequate reverse cholesterol transport is a significant contributor to inflammation. Additionally, metabolic stress induced by nutritional overload can activate the unfolded protein response in the ER, further exacerbating low-grade chronic inflammation linked to various metabolic disorders. The chapter concludes by examining the microbiome's role in modulating immune responses throughout life, emphasizing how nutrient-triggered interactions shape this dynamic relationship.