| Summary: | In individuals with lymphedema, diabetic foot, or other diseases, infections with saprophytes are common. The response of major cell subpopulations in the draining lymph nodes to skin infection with <i>Staphylococcus epidermidis</i> was assessed using the rat model. After massive subepidermal infection, a cytometric evaluation showed an increase in cytotoxic and helper T lymphocytes and major subpopulations of the innate immune response. Three weeks later, signs of inflammation reduction with an increase in the content of memory T helper lymphocytes and effector memory T cytotoxic lymphocytes were observed. After skin re-infection, a rapid response of cytotoxic, helper, and memory T lymphocytes, memory B lymphocytes and plasmablasts, and macrophages was detected. In addition, a reduction in the number of naïve B lymphocytes, activated MHC class II+ cells, and some cells of the innate immune system was observed. T regulatory lymphocyte response after the initial and secondary <i>S. epidermidis</i> skin infection was not detected. The morphometric evaluation showed significant changes in the main cell subpopulations in each functional zone of the node and then confirmed the efficient elimination of the administered antigen, as evidenced by the observations on day 28. Notably, after re-infection, the cellular response did not exceed the level after the initial infection and was reduced in many cell subpopulations. Understanding how the lymph nodes eliminate <i>S. epidermidis</i> can provide valuable insights into creating immunological therapies against infections with saprophytes.
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