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Metabolic immunomodulation of macrophage functional plasticity in nonhealing wounds

Anders, Catherine B.; Lawton, Tyler M.W.; Ammons, Mary Cloud B.

Current Opinion in Infectious Diseases: June 2019 - Volume 32 - Issue 3 - p 204–209
doi: 10.1097/QCO.0000000000000550
PATHOGENESIS AND IMMUNE RESPONSE: Edited by Dennis L. Stevens and Dimitri A. Diavatopoulos

Purpose of review Despite modern advances in medicine, nonhealing wounds are the number one cause of nontraumatic, lower-limb amputation. Nonhealing wounds are characterized by a healing process stalled between inflammation and tissue remodel/repair, a stage characterized by a shift in macrophage functional phenotype. Characterization of diversity in macrophage functional phenotype in wounds and metabolic contributions to macrophage polarization are discussed.

Recent findings Macrophage functional diversity in phenotype has recently evolved from duality (classically activated, pro-inflammatory M1 and alternatively activated, anti-inflammatory M2) to include an additional four alternately activated subphenotypes (M2a, M2b, M2c and M2d). Metabolic pathway utilization shifts characterize macrophage polarization with resulting metabolic and immune outcomes impacting host–pathogen interactions during wound healing.

Summary Recognition of the key role macrophage diversity plays in wound healing, along with better characterization of diverse macrophage phenotypes, will inform our understanding of pathogenicity in wound healing. Comprehensive profiling of the metabolism regulating macrophage polarization and host–pathogen interaction creates opportunity of discovery for innovative new diagnostics and therapeutics for treating nonhealing wounds.

Idaho Veterans Research & Education Foundation (IVREF) – Boise VA Medical Center (BVAMC), Boise, Idaho, USA

Correspondence to Mary Cloud B. Ammons, Mail Stop 151, Building 117, 500 West Fort Street, Boise, ID 83702, USA. Tel: +1 208 422 1219; e-mail:;

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