title: MyD88 in macrophages is critical for abscess resolution in staphylococcal skin infection.
abstract: When Staphylococcus aureus penetrates the epidermis and reaches the dermis, polymorphonuclear leukocytes (PMLs) accumulate and an abscess is formed. However, the molecular mechanisms that orchestrate initiation and termination of inflammation in skin infection are incompletely understood. In human myeloid differentiation primary response gene 88 (MyD88) deficiency, staphylococcal skin and soft tissue infections are a leading and potentially life-threatening problem. In this study, we found that MyD88-dependent sensing of S. aureus by dermal macrophages (Mϕ) contributes to both timely escalation and termination of PML-mediated inflammation in a mouse model of staphylococcal skin infection. Mϕs were key to recruit PML within hours in response to staphylococci, irrespective of bacterial viability. In contrast with bone marrow-derived Mϕs, dermal Mϕs did not require UNC-93B or TLR2 for activation. Moreover, PMLs, once recruited, were highly activated in an MyD88-independent fashion, yet failed to clear the infection if Mϕs were missing or functionally impaired. In normal mice, clearance of the infection and contraction of the PML infiltrate were accompanied by expansion of resident Mϕs in a CCR2-dependent fashion. Thus, whereas monocytes were dispensable for the early immune response to staphylococci, they contributed to Mϕ renewal after the infection was overcome. Taken together, MyD88-dependent sensing of staphylococci by resident dermal Mϕs is key for a rapid and balanced immune response, and PMLs are dependent on intact Mϕ for full function. Renewal of resident Mϕs requires both local control of bacteria and inflammatory monocytes entering the skin.
authors: Center for Chronic Immunodeficiency, University Medical Center, University of Freiburg, 79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany;
authors: Reinhild
authors: R
authors: Feuerstein
authors: Center for Chronic Immunodeficiency, University Medical Center, University of Freiburg, 79106 Freiburg, Germany; Institute of Pathology, University Medical Center, University of Freiburg, 79106 Freiburg, Germany;
authors: Maximilian
authors: M
authors: Seidl
authors: Institute of Neuropathology, University Medical Center, University of Freiburg, 79106 Freiburg, Germany; Centre of Biological Signalling Studies, University of Freiburg, 79106 Freiburg, Germany; and.
authors: Marco
authors: M
authors: Prinz
authors: Center for Chronic Immunodeficiency, University Medical Center, University of Freiburg, 79106 Freiburg, Germany; Center for Pediatrics and Adolescent Medicine, University Medical Center, University of Freiburg, 79106 Freiburg, Germany philipp.henneke@uniklinik-freiburg.de.
authors: Philipp
authors: P
authors: Henneke
mesh_terms: D000038:Abscess / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology* / Q000502:physiology
chemical_list: D000950:Antigens, Ly; C515335:Ccr2 protein, mouse; C494192:Ly-6C antigen, mouse; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D054390:Receptors, CCR2