Malnutrition, which encompasses under- and overnutrition, is responsible for an enormous morbidity and mortality burden globally. Malnutrition results from disordered nutrient assimilation but is also characterized by recurrent infections and chronic inflammation, implying an underlying immune defect. Defects emerge before birth via modifications in the immunoepigenome of malnourished parents, and these may contribute to intergenerational cycles of malnutrition. This review summarizes key recent studies from experimental animals, in vitro models, and human cohorts, and proposes that immune dysfunction is both a cause and a consequence of malnutrition. Focusing on childhood undernutrition, we highlight gaps in current understanding of immune dysfunction in malnutrition, with a view to therapeutically targeting immune pathways as a novel means to reduce morbidity and mortality.
Undernourished children principally die of common infections, and immune defects are consistently demonstrated in under- and overnutrition.
Parental malnutrition leads to epigenetic modifications of infant immune and metabolic genes.
Healthy gut development relies on sensing of dietary nutrients, commensal, and pathogenic microbes via immune receptors.
Recurrent infections, chronic inflammation, and enteropathy compound clinical malnutrition by altering gut structure and function.
Immune cell activation and systemic proinflammatory mediator levels are increased in malnutrition.
Malnutrition impairs immune priming by DC and monocytes, and impairs effector memory T cell function.
Immune dysfunction can directly drive pathological processes in malnutrition, including malabsorption, increased metabolic demand, dysregulation of the growth hormone and HPA axes, and greater susceptibility to infection.