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

Authors


* Robert D. Stout
Department of Microbiology and Immunology
University of Louisville School of Medicine
Health Sciences Center
Building 55A
Louisville, KY 40292
USA
Tel.: +1 502 852 5351
Fax: +1 502 852 7531
E-mail: bobstout@louisville.edu

Abstract

Summary:  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.

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