Aging of the innate immune system

Abstract

The innate immune system is composed of a network of cells including neutrophils, NK and NKT cells, monocytes/macrophages, and dendritic cells that mediate the earliest interactions with pathogens. Age-associated defects are observed in the activation of all of these cell types, linked to compromised signal transduction pathways including the Toll-like Receptors. However, aging is also characterized by a constitutive pro-inflammatory environment (inflamm-aging) with persistent low-grade innate immune activation that may augment tissue damage caused by infections in elderly individuals. Thus, immunosenescence in the innate immune system appears to reflect dysregulation, rather than exclusively impaired function.

Figure 1. Consequences of altered membrane lipid content for neutrophil function

Studies of peritoneal neutrophils from aged rats [13] have shown reduced levels of cholesterol and increased membrane fluidity, associated with reduced superoxide generating ability. Other studies have shown dysregulation of receptor recruitment to lipid rafts, which will have very broad effects in compromising receptor signaling functions and downstream biological effects. Abbreviations: PKB, protein kinase B; PI3K, phosphoinositide-3-kinase; JAK, JAK, JAK-STAT signaling (JAK, Janus kinase; STAT Signal Transducers and Activators of Transcription).