Protective immunity in recurrent Staphylococcus aureus infection reflects localized immune signatures and macrophage-conferred memory

and the MRSA Systems Immunobiology Group

Research output: Contribution to journalArticle

Abstract

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 protective innate memory against recurrent methicillin-resistant S. aureus (MRSA) SSSI. In the present study, the dynamics and mechanisms of this response were explored in recurrent SSSI in WT mice. Priming by prior infection reduced skin lesion severity and MRSA burden, and protected against dissemination at day 7 but not day 2. Cytokine and cellular signatures in SSSI differed at day 2 versus 7, and were distinct in skin versus blood or spleen. Cytokines associated with protection in skin included increased IL-17, IL-6, monokine inducible by IFN-γ (MIG), and RANTES, while increased IP-10 correlated with protection from dissemination. Cellular signatures of protection included increased Th17, M1 macrophage, and dendritic cell populations in abscesses, and total macrophages in lymph nodes. Priming potentiated S. aureus-specific phagocytic killing by bone marrow-derived macrophages in vitro, and their adoptive transfer into naïve skin afforded protective efficacy in vivo. Present findings indicate that protective immunity in recurrent S. aureus infection is locally targeted, and involves specific memory conferred by macrophages. These insights provide targets for vaccine and immunotherapeutic development against MRSA.

Original languageEnglish (US)
Pages (from-to)E11111-E11119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number47
DOIs
StatePublished - Nov 20 2018

Keywords

  • Adoptive transfer
  • Innate immune memory
  • Macrophage
  • Recurrent skin infection
  • Staphylococcus aureus

ASJC Scopus subject areas

  • General

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