Immunity & infection
Staphylococcus aureus is the leading cause of skin and skin structure infection (SSSI), a primary portal of entry for invasive infection. Our prior studies discovered a role for innate immune memory in protection against recurrent methicillin-resistant S. aureus (MRSA) SSSI. Priming infection 6 weeks earlier resulted in protective memory upon recurrent infection in wild-type and rag1-/- mice. To test durability of this memory, we infected wild-type mice one year prior to secondary challenge. Eight-week old mice were infected with MRSA subcutaneously, allowed to resolve for one year, and infected again with the identical MRSA strain. Lesion sizes were measured on days 1, 3, 5 & 7 post-secondary challenge and MRSA were enumerated in skin abscesses, kidney, spleen and liver on day 7. Remarkably, primed mice exhibited protective memory in skin, manifest as reduced lesion sizes and MRSA burden in abscesses during secondary MRSA challenge. However, there was no protection against disseminated infection, as similar MRSA burden was observed in the kidney, spleen and liver. Cellular signatures of protection were represented by increased numbers of monocytes and NK cells in abscesses, and monocyte intensification in lymph nodes. As expected, cell populations in the spleen were similar. In summary, present findings indicate that protective immunity to S. aureus infection is tissue-targeted, involves monocytes and NK cells, and durable. These insights enhance understanding of mechanisms of immune protection vs. S. aureus, and may hold novel targets for vaccine and immunotherapeutic development against MRSA.