Immunity & infection
Staphylococcus aureus is the leading cause of skin and skin structure infection (SSSI), a primary portal of entry for invasion. Our previous studies discovered a role for protective immune memory against methicillin-resistant S. aureus (MRSA) SSSI. Prior infection (priming) protected against localized and disseminated infection at day 7 post-infection (late) in SSSI, but not at day 2 (early). Protective cytokines in skin included increased IL-17, IL-6, MIG and RANTES, while increased IP-10 correlated with protection from dissemination. Here, we characterized evolution of cellular immunity over time (early vs. late) and space (skin abscess; draining inguinal lymph node [iLN]; spleen) in naïve versus primed mice during MRSA SSSI. Early CD4+ Th1 and Th17, and CD8+ T cell subset infiltration in skin, relative to CD4+ subset egress from iLN, corresponded to protection in abscesses of primed mice. Early and late M1 macrophage (Mf) accumulation in skin and iLN correlated with protection in abscesses. In the spleen, priming resulted in gd-T, NK, ILC1 and dendritic cell accumulation during early SSSI. However, Th17, ILC2 and ILC3 populations dominated during late infection, corresponding to protection in the spleen. Together, these findings indicate that priming induces sustained T cell and M1 Mf responses in skin, but late ILC responses in spleen correlating with protective immune memory. This pattern of results reveals coordinated temperospatial evolution of cellular immune memory during MRSA infection. Such immune cell signatures likely synergize with other immune effectors in respective tissues. These insights provide new targets for vaccine and immunotherapeutic strategies against MRSA.