Immunosenescence and macrophage functional plasticity: dysregulation of macrophage function by age‐associated microenvironmental changes

Abstract

The macrophage lineage displays extreme functional and phenotypic heterogeneity, which appears to be because, in large part, of the ability of macrophages to functionally adapt to changes in their tissue microenvironment. This functional plasticity of macrophages plays a critical role in their ability to respond to tissue damage and/or infection and to contribute to clearance of damaged tissue and invading microorganisms, to recruitment of the adaptive immune system, and to resolution of the wound and of the immune response. Evidence has accumulated that environmental influences, such as stromal function and imbalances in hormones and cytokines, contribute significantly to the dysfunction of the adaptive immune system. The innate immune system also appears to be dysfunctional in aged animals and humans. In this review, the hypothesis is presented and discussed that the observed age-associated 'dysfunction' of macrophages is the result of their functional adaptation to the age-associated changes in tissue environments. The resultant loss of orchestration of the manifold functional capabilities of macrophages would undermine the efficacy of both the innate and adaptive immune systems. The macrophages appear to maintain functional plasticity during this dysregulation, making them a prime target of cytokine therapy that could enhance both innate and adaptive immune systems.

IL-2/CD40-activated macrophages rescue age and tumor-induced T cell dysfunction in elderly mice

“…These data are also in agreement with studies suggesting that cytokines improve function of macrophages in the elderly (Hayakawa et al 1995;Stout and Suttles 2005). Our data showed that use of an IL-2/anti-CD40 Ab-based immunotherapy could be effective in elderly cancer-bearing hosts.…”

Lack of CD47 on nonhematopoietic cells induces split macrophage tolerance to CD47nullcells

“…Tissue macrophages that are differentiated from the same precursor cells exhibit extensive variation in functions depending on their anatomic locations, and the maintenance of tissuespecific characteristics of macrophages is required for an organ to function normally (1,12,13). Residential intestinal macrophages display inflammatory anergy characterized by downregulated expression of innate response and growth factor receptors and reduced production of inflammatory cytokines but remain highly phagocytic (14)(15)(16).…”

Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum improves phagocytic potential of macrophages in aged mice

“…In aged people, the decline in phagocytic activity is associated with increased susceptibility to infectious agents that contributes to infectioninduced morbidity and mortality (Makinodan 1981). A reduction in number of phagocytes coupled with an intrinsic decline of their bactericidal activity has been observed in aged people (Strout and Suttles 2005). Also, there is a significant reduction in production of reactive oxygen intermediate (ROI) species in phagocytic cells (PMNs) in elderly.…”