Human Macrophage Response To Bacterial And Fungal Isolates From Diabetic Foot Ulcers
Carly Deusenbery1, Anamika Bajpai, PhD1, Lindsay Kalan, PhD2, Jacquelyn S. Meisel2, Brandon Marcinkiewicz, MS1, Sue E. Gardner, PhD3, Elizabeth Grice, PhD2, Kara L. Spiller, PhD1.
1Drexel University, Philadelphia, PA, USA, 2University of Pennsylvania, Philadelphia, PA, USA, 3University of Iowa, Iowa City, IA, USA.
BACKGROUND - In diabetic foot ulcers (DFUs) the wound environment is in continuous contact with colonizing microbes, which have potential to modify healing responses and/or cause clinical infection. Macrophages, the primary innate immune cells, kill infiltrating pathogens and modulate the local micro-environment. As modulators of their environment, macrophages are multifunctional, interacting with their environment and eliciting changes their behavior to regulate the diverse processes of wound healing. METHODS - To better understand the response of macrophages to the colonizing microbiota, conditioned media from bacterial and fungal isolates from DFUs were added to primary human macrophages for 24 hours, in vitro. Analysis of macrophage gene expression and protein production showed that both markers of pro-inflammatory M1 and wound-resolving M2 phenotypes were upregulated to different extents by five bacterial and one fungal species. RESULTS - Specifically, Corynebacterium amycolatum, Corynebacterium striatum, and Pseudomonas aeruginosa conditioned media promoted macrophages to increase secretion of PDGF-BB, a cytokine involved in ECM deposition along with pro-inflammatory cytokines VEGF, IL1β, and TNFα, relative to unactivated M0 and M1 macrophage controls, collectively suggesting a fibrotic response. CONCLUSION - Therefore, these data indicate irregularities in macrophage behavior to different colonizing microbes, suggesting that the microbiome of patients could be used as an indicator for tailored chronic wound treatments. Investigation of the unique responses of macrophage to colonizing microbiota could be used to engineer chronic wound solutions that address the macrophage deficits.
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