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Macrophages, the primary innate immune cells, are multifunctional cells that regulate diverse processes throughout multiple phases of wound healing. To better understand the influence of microbial species on macrophage behavior, we cultured primary human monocyte\u2010derived macrophages from four donors for 24\u2009hours in media conditioned by bacteria and fungi (<jats:italic>Pseudomonas aeruginosa<\/jats:italic>, <jats:italic>Corynebacterium amycolatum<\/jats:italic>, <jats:italic>Corynebacterium striatum<\/jats:italic>, <jats:italic>Staphylococcus aureus<\/jats:italic>, <jats:italic>Staphylococcus simulans<\/jats:italic>, and <jats:italic>Candida albicans<\/jats:italic>) isolated from the DFUs of six patients. The effects of these microbe\u2010derived signals on macrophage behavior were assessed by measuring the gene expression of a panel of 25 genes related to macrophage phenotype, angiogenesis, bacterial recognition, and cell survival, as well as secretion of two inflammatory cytokines using NanoString multiplex analysis. Principal component analysis showed that macrophage gene expression and protein secretion were affected by both microbial species as well as human donor. <jats:italic>S<\/jats:italic>. <jats:italic>simulans<\/jats:italic> and <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic> caused up\u2010regulation of genes associated with a proinflammatory (M1) phenotype, and <jats:italic>P<\/jats:italic>. <jats:italic>aeruginosa<\/jats:italic> caused an increase in the secretion of the proinflammatory cytokine and M1 marker tumor necrosis factor\u2010alpha (TNF\u03b1). Together, these results suggest that macrophages respond to secreted factors from microbes by up\u2010regulating inflammatory markers, and that the effects are strongly dependent on the monocyte donor. Ultimately, increased understanding of macrophage\u2013microbe interactions will lead to the development of more targeted therapies for DFU healing.<\/jats:p>","DOI":"10.1111\/wrr.12752","type":"journal-article","created":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T12:48:08Z","timestamp":1564058888000},"page":"598-608","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Human macrophage response to microbial supernatants from diabetic foot ulcers"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6931-3812","authenticated-orcid":false,"given":"Carly B.","family":"Deusenbery","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering Science and Health Systems Drexel University  Philadelphia 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