Protective immunity in recurrent Staphylococcus aureus infection reflects localized immune signatures and macrophage-conferred memory
| Autor: | Liana C, Chan, Maura, Rossetti, Lloyd S, Miller, Scott G, Filler, Colin W, Johnson, Hong K, Lee, Huiyuan, Wang, David, Gjertson, Vance G, Fowler, Elaine F, Reed, Michael R, Yeaman |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Methicillin-Resistant Staphylococcus aureus medicine.medical_treatment Staphylococcus 030106 microbiology Spleen medicine.disease_cause 03 medical and health sciences Interferon-gamma Mice Immune system Commentaries Medicine Macrophage Animals Chemokine CCL5 Homeodomain Proteins Mice Knockout Multidisciplinary business.industry Skin and skin structure infection Interleukin-6 Macrophages Interleukin-17 Dendritic cell Dendritic Cells Adoptive Transfer Immunity Innate Monokine Chemokine CXCL10 Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Cytokine PNAS Plus Staphylococcus aureus Immunology Th17 Cells Staphylococcal Skin Infections business Immunologic Memory |
| Popis: | 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 naive 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. |
| Databáze: | OpenAIRE |
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