title: Coevolution of markers of innate and adaptive immunity in skin and peripheral blood of patients with erythema migrans.
abstract: We used multiparameter flow cytometry to characterize leukocyte immunophenotypes and cytokines in skin and peripheral blood of patients with erythema migrans (EM). Dermal leukocytes and cytokines were assessed in fluids aspirated from epidermal suction blisters raised over EM lesions and skin of uninfected controls. Compared with corresponding peripheral blood, EM infiltrates were enriched for T cells, monocytes/macrophages, and dendritic cells (DCs), contained lower proportions of neutrophils, and were virtually devoid of B cells. Enhanced expression of CD14 and HLA-DR by lesional neutrophils and macrophages indicated that these innate effector cells were highly activated. Staining for CD45RO and CD27 revealed that lesional T lymphocytes were predominantly Ag-experienced cells; furthermore, a subset of circulating T cells also appeared to be neosensitized. Lesional DC subsets, CD11c(+) (monocytoid) and CD11c(-) (plasmacytoid), expressed activation/maturation surface markers. Patients with multiple EM lesions had greater symptom scores and higher serum levels of IFN-alpha, TNF-alpha, and IL-2 than patients with solitary EM. IL-6 and IFN-gamma were the predominant cytokines in EM lesions; however, greater levels of both mediators were detected in blister fluids from patients with isolated EM. Circulating monocytes displayed significant increases in surface expression of Toll-like receptor (TLR)1 and TLR2, while CD11c(+) DCs showed increased expression of TLR2 and TLR4; lesional macrophages and CD11c(+) and CD11c(-) DCs exhibited increases in expression of all three TLRs. These results demonstrate that Borrelia burgdorferi triggers innate and adaptive responses during early Lyme disease and emphasize the interdependence of these two arms of the immune response in the efforts of the host to contain spirochetal infection.
authors.affiliation: Department of Pediatrics, Division of Pediatric Infectious Diseases, Connecticut Children's Medical Center, 282 Washington Street, Hartford, CT 06106, USA. jsalaza@ccmckids.org
authors.forename: Juan C
authors.initials: JC
authors.lastname: Salazar
authors.forename: Constance D
authors.initials: CD
authors.lastname: Pope
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Sellati
authors.forename: Henry M
authors.initials: HM
authors.lastname: Feder
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Kiely
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Dardick
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Buckman
authors.forename: Meagan W
authors.initials: MW
authors.lastname: Moore
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Caimano
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Pope
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Krause
authors.forename: Justin D
authors.initials: JD
authors.lastname: Radolf
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001768:Blister / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D025065:Borrelia burgdorferi / Q000276:immunology / Q000302:isolation & purification; D002465:Cell Movement / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015787:Erythema Chronicum Migrans / Q000097:blood* / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000097:blood; D008875:Middle Aged; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000097:blood; D012867:Skin / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D015415:Biomarkers; D016207:Cytokines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors