Staphylococcus aureus is a human commensal that colonizes the skin. While it is normally innocuou... more Staphylococcus aureus is a human commensal that colonizes the skin. While it is normally innocuous, it has strong associations with atopic dermatitis pathogenesis, and has become the leading cause of skin and soft tissue infections in the USA. The factors that dictate the role of S. aureus in disease are still being determined. In this work, we utilized primary keratinocyte culture and an epidermal murine colonization model to investigate the role of S. aureus phenol soluble modulins (PSMs) on pro-inflammatory cytokine release and inflammation induction. We demonstrated that many species of Staphylococcus are capable of causing release of IL-18 from keratinocytes and that S. aureus PSMs are necessary and sufficient to stimulate IL-18 release from keratinocytes independent of caspase-1. Further, after seven days of epicutaneous exposure to wild type S. aureus, but not Δpsm S. aureus, we saw dramatic changes in gross pathology as well as systemic release of pro-inflammatory cytokines....
Beyond their critical role in humoral immunity, B lymphocytes can employ a variety of immunomodul... more Beyond their critical role in humoral immunity, B lymphocytes can employ a variety of immunomodulatory mechanisms including expression of the apoptosis-inducing molecule Fas ligand (FasL; CD178). Here, we extensively characterized the surface phenotype of FasL(+) killer B cells, showing they are enriched in the IgM(high)CD5(+)CD1d(high) B cell subset previously reported to contain a higher frequency of B cells producing interleukin-10 (IL-10). A rare population of B cells expressing IL-10 was present among FasL(+) B cells, but most FasL(+) B cells did not produce IL-10. We also identify interleukin-5 (IL-5) as a novel inducer of killer B cell function. Constitutively FasL(+) B cells expressed higher levels of the IL-5 receptor, and treating B cells with IL-5 and CD40L resulted in the expansion of a B cell population enriched for FasL(+) cells. B cells stimulated with IL-5 and CD40L were potent inducers of apoptosis in activated primary CD4(+) T cells, and this killing function was a...
Staphylococcus aureus is a human commensal that colonizes the skin. While it is normally innocuou... more Staphylococcus aureus is a human commensal that colonizes the skin. While it is normally innocuous, it has strong associations with atopic dermatitis pathogenesis, and has become the leading cause of skin and soft tissue infections in the USA. The factors that dictate the role of S. aureus in disease are still being determined. In this work, we utilized primary keratinocyte culture and an epidermal murine colonization model to investigate the role of S. aureus phenol soluble modulins (PSMs) on pro-inflammatory cytokine release and inflammation induction. We demonstrated that many species of Staphylococcus are capable of causing release of IL-18 from keratinocytes and that S. aureus PSMs are necessary and sufficient to stimulate IL-18 release from keratinocytes independent of caspase-1. Further, after seven days of epicutaneous exposure to wild type S. aureus, but not Δpsm S. aureus, we saw dramatic changes in gross pathology as well as systemic release of pro-inflammatory cytokines....
Beyond their critical role in humoral immunity, B lymphocytes can employ a variety of immunomodul... more Beyond their critical role in humoral immunity, B lymphocytes can employ a variety of immunomodulatory mechanisms including expression of the apoptosis-inducing molecule Fas ligand (FasL; CD178). Here, we extensively characterized the surface phenotype of FasL(+) killer B cells, showing they are enriched in the IgM(high)CD5(+)CD1d(high) B cell subset previously reported to contain a higher frequency of B cells producing interleukin-10 (IL-10). A rare population of B cells expressing IL-10 was present among FasL(+) B cells, but most FasL(+) B cells did not produce IL-10. We also identify interleukin-5 (IL-5) as a novel inducer of killer B cell function. Constitutively FasL(+) B cells expressed higher levels of the IL-5 receptor, and treating B cells with IL-5 and CD40L resulted in the expansion of a B cell population enriched for FasL(+) cells. B cells stimulated with IL-5 and CD40L were potent inducers of apoptosis in activated primary CD4(+) T cells, and this killing function was a...
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Papers by Tamra J Reed