Basophil, eosinophil, and neutrophil functions in the elderly

Abstract

Human granulocytes are classically characterized by their capacity to act as phagocytes, degranulators secreting preformed lytic enzymes from their granules, and produce reactive oxygen species (ROS) to destroy bacteria, parasites, and fungi. Basophils and eosinophils are mainly involved in the defense against parasites or allergic reactions, but also they play important roles in antigen presentation, immune memory response, and T helper 2 cell (Th2) differentiation. Like basophils and eosinophils, neutrophils and their function have been underestimated in research for a long time. Thus, neutrophils have been categorized as short-lived phagocytic cells of the innate immune system with limited ability for biosynthetic activity and being the first cells appearing in inflamed locations/acute inflammation to fight extracellular pathogens. In the last two decades, this limited view was challenged by the demonstration that neutrophils survive much longer than first suggested and can be induced to de novo express genes encoding key inflammatory mediators, including complement components, Fc receptors, chemokines, and cytokines. Immune cells of the innate and the adaptive system are uniformly compromised by aging, contributing to the high susceptibility to infections and increased mortality observed in the elderly. Whereas the effects of aging on T and B cells of the adaptive immune system are well documented, studies related to age-related defects of polymorphonuclear neutrophils (PMN), basophils, and eosinophils are restricted. That is surprising since genetically induced immune defects of, e.g., neutrophils increase susceptibility to severe infections and mortality. Furthermore, during aging there is a shift from the adaptive immune to the innate system which raises the importance of these cells. There is consensus about unchanged neutrophil numbers in the circulation throughout aging; apart from this, reports about changes in tissue infiltration, phagocytosis, and burst capabilities of neutrophils from aged donors are inconsistent. Additionally, there are many different results between in vivo and in vitro studies as well as between studies investigating murine and human neutrophils. The majority of the reported discrepancies in neutrophils during aging function originate from damaged signaling pathways and studies where the SENIEUR protocol has not been used. Research in neutrophils, in addition, would build the basis for drug development in preventing and/or fighting age-related diseases. Research on human basophils and eosinophils and their function during aging is rare despite the fact that these cells are important in defense against parasites and play an important role in allergy, asthma, and autoimmune diseases. This chapter highlights the age-related changes of the immune system, focusing on new insights into neutrophil, basophil, and eosinophil immunity.