Resident macrophages acquire innate immune memory in staphylococcal skin infection
Open accessAbstract
Staphylococcus aureus (S. aureus) is a common colonizer of healthy skin and mucous membranes. At the same time, S. aureus is the most frequent cause of skin and soft tissue infections. Dermal macrophages (Mφ) are critical for the coordinated defense against invading S. aureus, yet they have a limited life span with replacement by bone marrow derived monocytes. It is currently poorly understood whether localized S. aureus skin infections persistently alter the resident Mφ subset composition and resistance to a subsequent infection. In a strictly dermal infection model we found that mice, which were previously infected with S. aureus, showed faster monocyte recruitment, increased bacterial killing and improved healing upon a secondary infection. However, skin infection decreased Mφ half-life, thereby limiting the duration of memory. In summary, resident dermal Mφ are programmed locally, independently of bone marrow-derived monocytes during staphylococcal skin infection leading to transiently increased resistance against a second infection.
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Effector T cells play a critical role in the host's defense during reinfection with C. albicans, Staphylococcus aureus, Leishmania major, and HSV.
“Effector T cells play a critical role in the host’s defense during reinfection with C. albicans, Staphylococcus aureus, Leishmania major, and HSV [28,30–35].”
From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [28]
In Results (‘Infection-induced resistance against S. aureus does not depend on bone marrow-derived monocytes and on mature T, B, and NK cells’; page unavailable), the paper reports enhanced protection on re-exposure in mice lacking mature T cells. It concludes that this protection does not depend on the adaptive immune system, contrary to the claim that effector T cells are critical for defense against S. aureus reinfection. The paper does not test T-cell protection against the other named pathogens. (LLM, conf=0.90)
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Experimental — accuracy not yet measuredCcr2-/- mice are defective in recruiting inflammatory macrophages and moDCs to the site of infection.
“we utilized Ccr2-/- mice that are defective in recruiting inflammatory macrophages and moDCs to the site of infection [28].”
From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [28]
The Results section on infection-induced resistance reports that the infection-associated rise in Ly6Chi dermal macrophages was absent in Ccr2-/- mice, supporting defective recruitment of inflammatory macrophages. The cited paper does not establish the claimed defect in recruiting monocyte-derived dendritic cells (moDCs). No page numbers are provided in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredDepletion of IL-12-producing inflammatory macrophages and monocyte-derived dendritic cells with clodronate liposome or in Ccr2−/− mice decreases IL-12 production and Th1 cell development in vivo.
“Indeed, depletion of these populations with clodronate liposome or Ccr2−/− mice decreased IL-12 production and Th1 cell development in vivo [122].”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [122]
The Results section, “Resident dermal Mφ mediate innate memory” (page not available), reports that clodronate liposomes depleted resident dermal macrophages. The Results section on infection-induced resistance (page not available) reports reduced inflammatory monocytes in Ccr2−/− mice. Neither passage reports depletion of monocyte-derived dendritic cells or a decrease in IL-12 production or Th1-cell development; the measured outcomes were bacterial killing, infiltrating cells, and IL-1β. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIL-12-producing inflammatory macrophages and monocyte-derived dendritic cells are the key sources of IFN-γ-inducing signals during C. auris re-infection.
“At the cellular level, IL-12-producing inflammatory macrophages and monocyte-derived dendritic cells are the key sources of IFN-γ-inducing signals during C. auris re-infection (Fig 4).”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [122]
The Results sections on dermal macrophage responses and secondary infection describe an S. aureus mouse model, not C. auris re-infection. Searches for IL-12, IFN-γ and monocyte-derived dendritic cells did not yield a passage identifying the claimed sources of IFN-γ-inducing signals. (LLM, conf=0.78)
Experimental — accuracy not yet measured
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Cited by
Sorted by citations
The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin
Das, D., Ganesh, S. M., Mishra, A., Netea, M. G., & Thangamani, S. (2025) · PLOS Pathogens · doi:10.1371/journal.ppat.1013114 · Cited by 18 · see citing works
Host–Candida auris interactions in the skin
Thangamani, S., Balakumar, A., Datta, A., Bryak, G., & Lionakis, M. S. (2026) · PLOS Pathogens · doi:10.1371/journal.ppat.1014075 · Cited by 3 · see citing works
- Authors
- Feuerstein, R., Forde, A. J., Lohrmann, F., Kolter, J., Ramirez, N. J., Zimmermann, J., Gomez de Agüero, M., & Henneke, P.
- Affiliations
- University of Freiburg (DE)
- University of Bern (CH)
- Maurice Müller Laboratories (Department for Biomedical Research), Universitätsklinik für Viszerale Chirurgie und Medizin Inselspital, University of Bern, Bern, Switzerland
- Corresponding author
- Henneke, Philipp
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2020-07-08
- Volume
- 9
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC7343389
- OpenAlex
- W3041772921
- Cited by
- 46
- References
- 2
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 6 · 2023: 11 · 2022: 4 · 2021: 10 · 2020: 2
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Open Access CRIS of the University of Bern
- Funders
- Deutsche Forschungsgemeinschaft (HE3127/9, HE3127/12, SFB/TRR167)
- Bundesministerium für Bildung und Forschung (01EO0803, 01GL1746A, 01EK1602A)
- Else Kröner-Fresenius Foundation
- H2020 Marie Skłodowska-Curie Actions (744257)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Ambizione PZOOP3_168012)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- Staphylococcus aureus, skin infections, dermal macrophages, trained immunity, monocyte recruitment, skin colonization, bacterial clearance, wound healing
- MeSH terms
- Animals, Disease Models, Animal, Female, Immunity, Innate, Immunologic Memory, Macrophages, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Monocytes, Staphylococcal Skin Infections, Staphylococcus aureus, Mice
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