4.6 Review

Timing is everything: impact of development, ageing and circadian rhythm on macrophage functions in urinary tract infections

Journal

MUCOSAL IMMUNOLOGY
Volume 15, Issue 6, Pages 1114-1126

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1038/s41385-022-00558-z

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Funding

  1. Columbia University O'Brien Center Opportunity Pool [U54DK104309-08]
  2. National Health and Medical Research Council of Australia (NHMRC) Investigator Grant [APP1194406]
  3. NIH [R01DK100644, R01AG052494, P20DK119840, R56AG064634]

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This review examines the diverse functional roles of macrophages in the bladder, including clearance of cell debris, immune surveillance, and inflammatory responses. It also focuses on the origins, differentiation, recruitment, and engagement of macrophages in host defense against urinary tract infections. Additionally, the review explores the influence of age on macrophage functions and the role of diurnal variations in host defense and inflammation.
The bladder supports a diversity of macrophage populations with functional roles related to homeostasis and host defense, including clearance of cell debris from tissue, immune surveillance, and inflammatory responses. This review examines these roles with particular attention given to macrophage origins, differentiation, recruitment, and engagement in host defense against urinary tract infections (UTIs), where these cells recognize uropathogens through a combination of receptor-mediated responses. Time is an important variable that is often overlooked in many clinical and biological studies, including in relation to macrophages and UTIs. Given that ageing is a significant factor in urinary tract infection pathogenesis and macrophages have been shown to harbor their own circadian system, this review also explores the influence of age on macrophage functions and the role of diurnal variations in macrophage functions in host defense and inflammation during UTIs. We provide a conceptual framework for future studies that address these key knowledge gaps.

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