title: Complement modulates the cutaneous microbiome and inflammatory milieu.
abstract: The skin is colonized by a plethora of microbes that include commensals and potential pathogens, but it is currently unknown how cutaneous host immune mechanisms influence the composition, diversity, and quantity of the skin microbiota. Here we reveal an interactive role for complement in cutaneous host-microbiome interactions. Inhibiting signaling of the complement component C5a receptor (C5aR) altered the composition and diversity of the skin microbiota as revealed by deep sequencing of the bacterial 16S rRNA gene. In parallel, we demonstrate that C5aR inhibition results in down-regulation of genes encoding cutaneous antimicrobial peptides, pattern recognition receptors, and proinflammatory mediators. Immunohistochemistry of inflammatory cell infiltrates in the skin showed reduced numbers of macrophages and lymphocytes with C5aR inhibition. Further, comparing cutaneous gene expression in germ-free mice vs. conventionally raised mice suggests that the commensal microbiota regulates expression of complement genes in the skin. These findings demonstrate a component of host immunity that impacts colonization of the skin by the commensal microbiota and vice versa, a critical step toward understanding host-microbe immune mutualism of the skin and its implications for health and disease. Additionally, we reveal a role for complement in homeostatic host-microbiome interactions of the skin.
authors: Departments of Dermatology and Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors: Christel
authors: C
authors: Chehoud
authors: Stavros
authors: S
authors: Rafail
authors: Amanda S
authors: AS
authors: Tyldsley
authors: John T
authors: JT
authors: Seykora
authors: John D
authors: JD
authors: Lambris
authors: Elizabeth A
authors: EA
authors: Grice
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology*; D008969:Molecular Sequence Data; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000276:immunology* / Q000382:microbiology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D018836:Inflammation Mediators; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D044087:Receptor, Anaphylatoxin C5a; D051192:Receptors, Pattern Recognition; D003165:Complement System Proteins
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