title: High serum CXCL10 in Rickettsia conorii infection is endothelial cell mediated subsequent to whole blood activation.
abstract: The pathophysiological hallmark of Rickettsia conorii (R. conorii) infection comprises infection of endothelial cells with perivascular infiltration of T-cells and macrophages. Although interferon (IFN)-γ-induced protein 10 (IP-10)/CXCL10 is induced during vascular inflammation, data on CXCL10 in R. conorii infection is scarce.
  
  
  
  Serum CXCL10 was analyzed in two cohorts of southern European patients with R. conorii infection using multiplex cytokine assays. The mechanism of R. conorii-induced CXCL10 release was examined ex vivo using human whole blood interacting with endothelial cells.
  
  
  
  (i) At admission, R. conorii infected patients had excessively increased CXCL10 levels, similar in the Italian (n=32, ∼56-fold increase vs controls) and the Spanish cohort (n=38, ∼68-fold increase vs controls), followed by a marked decrease after recovery. The massive CXCL10 increase was selective since it was not accompanied with similar changes in other cytokines. (ii) Heat-inactivated R. conorii induced a marked CXCL10 increase when whole blood and endothelial cells were co-cultured. Even plasma obtained from R. conorii-exposed whole blood induced a marked CXCL10 release from endothelial cells, comparable to the levels found in serum of R. conorii-infected patients. Bacteria alone did not induce CXCL10 production in endothelial cells, macrophages or smooth muscle cells.
  
  
  
  We show a massive and selective serum CXCL10 response in R. conorii-infected patients, likely reflecting release from infected endothelial cells characterized by infiltrating T cells and monocytes. The CXCL10 response could contribute to T-cell infiltration within the infected organ, but the pathologic consequences of CXCL10 in clinical R. conorii infection remain to be defined.
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway. Electronic address: kari.otterdal@rr-research.no.
authors.forename: Kari
authors.initials: K
authors.lastname: Otterdal
authors.affiliation: Center of Rickettsioses and Arthropod-Borne Diseases, Department of Infectious Diseases, Hospital San Pedro-Center of Biomedical Research from La Rioja (CIBIR), C/Piqueras, 98, 26006 Logroño, La Rioja, Spain.
authors.forename: Aránzazu
authors.initials: A
authors.lastname: Portillo
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Faculty of Medicine, University of Oslo, PO Box 1078 Blindern, 0316 Oslo, Norway.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Astrup
authors.affiliation: Research Laboratory Nordland Hospital, P.O. Box 1480, 8092 Bodø, Norway.
authors.forename: Judith
authors.initials: J
authors.lastname: Ludviksen
authors.affiliation: Center of Excellence on Aging, University of Chieti, Via dei Polacchi, 66100 Chieti Scalo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Hospital for Rheumatic Diseases, Margrethe Grundtvigs vei 6, 2609 Lillehammer, Norway.
authors.forename: Sverre
authors.initials: S
authors.lastname: Holm
authors.affiliation: Center of Excellence on Aging, University of Chieti, Via dei Polacchi, 66100 Chieti Scalo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Santilli
authors.affiliation: Department of Clinical Medicine and Pathology, University of Palermo, Palermo 90133, Italy.
authors.forename: Giustina
authors.initials: G
authors.lastname: Vitale
authors.affiliation: Unité des Rickettsies, Université de la Mediterranée, 27 Blvd. Jean Moulin, 13385 Marseille, Cedex 05, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.affiliation: Department of Pathology, University of Texas Medical Branch, 301 University Blvd., Route 0428, Galveston, TX 77555-0428, USA.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Olano
authors.affiliation: Faculty of Medicine, University of Oslo, PO Box 1078 Blindern, 0316 Oslo, Norway; Department of Immunology, Oslo University Hospital Rikshospitalet, P.B. 4950 Nydalen, 0424 Oslo, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Schjalm
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Faculty of Medicine, University of Oslo, PO Box 1078 Blindern, 0316 Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, P.B. 4950 Nydalen, 0424 Oslo, Norway.
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.affiliation: Center of Rickettsioses and Arthropod-Borne Diseases, Department of Infectious Diseases, Hospital San Pedro-Center of Biomedical Research from La Rioja (CIBIR), C/Piqueras, 98, 26006 Logroño, La Rioja, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Oteo
authors.affiliation: Faculty of Medicine, University of Oslo, PO Box 1078 Blindern, 0316 Oslo, Norway; Research Laboratory Nordland Hospital, P.O. Box 1480, 8092 Bodø, Norway; Department of Immunology, Oslo University Hospital Rikshospitalet, P.B. 4950 Nydalen, 0424 Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, P.B. 4950 Nydalen, 0424 Oslo, Norway; Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, P.O. Box 6050 Langnes, 9037 Tromsø, Norway; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Faculty of Medicine, University of Oslo, PO Box 1078 Blindern, 0316 Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, P.B. 4950 Nydalen, 0424 Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Department of Immunology, Oslo University Hospital Rikshospitalet, P.B. 4950 Nydalen, 0424 Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, P.B. 4950 Nydalen, 0424 Oslo, Norway.
authors.forename: Per H
authors.initials: PH
authors.lastname: Nilsson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001907:Boutonneuse Fever / Q000097:blood* / Q000473:pathology; D054357:Chemokine CXCL10 / Q000096:biosynthesis*; D015331:Cohort Studies; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D020114:Rickettsia conorii; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10
keywords: CXCL10; IP-10; Inflammation; Mediterranean spotted fever; Rickettsia conorii