Th17 stimulation and IL17A play critical roles in the Staphylococcus aureus iron regulated surface determinant B (IsdB) mediated protection in a disseminated challenge model. (99.11)

Abstract We have previously shown that IsdB, a conserved protein expressed by Staphylococcus aureus, induces a robust antibody response which correlates with protection in a murine challenge model. Here we looked at IsdB mediated cellular immune response. First the importance of lymphocytes was examined. Using CB-17 SCID mice we noted that lymphocytes were essential in protection against disseminated S. aureus infection. Neither active nor passive IsdB immunization of CB-17 SCID mice conferred protection against a lethal challenge of S. aureus. Adoptive transfer of CD3+ plus B19+ cells conferred protection in CB-17 SCID immunized mice but not controls. Evaluation of lymphocyte subsets indicated that T cells but not B cells conferred protection. CD3+ or CD4+ T cells conferred protection, whereas CD8+ cells were less active. Neither CD19+ B cells nor CD138highB220intCD19lo plasma cells were protective. Supportive of this data, IsdB immunized Jh mice (IgH chain deficient) were protected against lethal challenge, while nude (T cell deficient) mice were not. In vitro assays indicated that isolated IsdB immune splenocytes produced abundant IL-17A, but not IFN-γ after in vitro stimulation with IsdB peptides. These findings suggest a role for Th 17 cells in IsdB mediated defense against invasive S. aureus infection.