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These infections can range from mild to potentially life\u2010threatening systemic illnesses progressing to bacteremia, endocarditis, and sepsis. Mast cells, traditionally recognized for their role in allergies, are highly abundant within the skin and are gaining recognition for their contribution to bacterial defense. Here, we discuss the role of mast cells in three models of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S.\u2009aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    skin infection according to skin depth: epicutaneous sensitization, intradermal injections, and subcutaneous injections. During\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S.\u2009aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    skin infection, mast cells become activated and accumulate in infected skin, recognize bacterial toxins, and modulate the activity of other immune cells, including neutrophils and dendritic cells. We discuss areas of research that should be the target of future studies, such as neuroimmunology, infected excisional wounds, and risk of systemic illness. Our review aims to bring attention to the host\u2013pathogen interaction between mast cells and\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S.\u2009aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    in the skin, both to encourage deeper investigation and inform the development of immunomodulatory\u2010based therapeutics.\n                  <\/jats:p>","DOI":"10.1111\/imcb.70155","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:10:11Z","timestamp":1786925411000},"page":"867-880","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mast Cells in Host Defense Against Cutaneous\n                    <i>Staphylococcus aureus<\/i>\n                    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