Sodium's multifaceted influence on macrophages and neutrophils

The immune system is responsible for the body’s homeostasis. On the one hand, it orchestrates a complex and dynamic defense against invading pathogens. On the other hand, it maintains a delicate balance to prevent self-intrinsic defects. Reaching the site of infection or inflammation, immune cells navigate through various microenvironments, adapting to diverse challenges. These environmental factors can impact immune cell function. Among them, high sodium (HS) environments have emerged as crucial determinants. This thesis addresses the interplay between elevated sodium levels and the activity of macrophages and neutrophils, shedding light on the repercussions for pathogen defense and resolution of inflammation. HS shifts macrophages’ polarization towards a more proinflammatory phenotype, boosting their antimicrobial activity. Our findings suggest that intracellular Na+ increase and hypertonic stress are both crucial but not sufficient for the HS-triggered effect in macrophages. HS environments also boost the bactericidal activity of monocytes and induce a proinflammatory phenotype in Tregs. However, contradictory data has been published on the impact of HS on neutrophils’ activity. Polymorphonuclear neutrophils (PMNs) are among the first cells being recruited to the site of infection or inflammation. Our data demonstrates that HS exposure attenuates the NADPH oxidase-dependent production of reactive oxygen species (ROS), resulting in impaired antibacterial activity of PMNs. PMNs are important for pathogen defense but are also known to cause tissue damage if their activity is not regulated properly. We, therefore, hypothesized that HS might orchestrate the immune response, fostering pathogen removal by macrophages but ensuring tissue integrity by dampening the activity of PMNs. This cell type-dependent modulation might promote the resolution of inflammation.