High serum CXCL10 in Rickettsia conorii infection is endothelial cell mediated subsequent to whole blood activation

Kari Otterdal; Aránzazu Portillo; Elisabeth Astrup; Judith Ludviksen; Giovanni Davì; Sverre Holm; Francesca Santilli; Giustina Vitale; Didier Raoult; Juan P Olano; Camilla Schjalm; Bente Halvorsen; José A Oteo; Tom Eirik Mollnes; Pål Aukrust; Per H Nilsson

doi:10.1016/j.cyto.2016.05.006

High serum CXCL10 in Rickettsia conorii infection is endothelial cell mediated subsequent to whole blood activation

Cytokine. 2016 Jul:83:269-274. doi: 10.1016/j.cyto.2016.05.006. Epub 2016 May 12.

Authors

Kari Otterdal¹, Aránzazu Portillo², Elisabeth Astrup³, Judith Ludviksen⁴, Giovanni Davì⁵, Sverre Holm⁶, Francesca Santilli⁵, Giustina Vitale⁷, Didier Raoult⁸, Juan P Olano⁹, Camilla Schjalm¹⁰, Bente Halvorsen¹¹, José A Oteo², Tom Eirik Mollnes¹², Pål Aukrust¹³, Per H Nilsson¹⁴

Affiliations

¹ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway. Electronic address: kari.otterdal@rr-research.no.
² 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.
³ 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.
⁴ Research Laboratory Nordland Hospital, P.O. Box 1480, 8092 Bodø, Norway.
⁵ Center of Excellence on Aging, University of Chieti, Via dei Polacchi, 66100 Chieti Scalo, Italy.
⁶ 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.
⁷ Department of Clinical Medicine and Pathology, University of Palermo, Palermo 90133, Italy.
⁸ Unité des Rickettsies, Université de la Mediterranée, 27 Blvd. Jean Moulin, 13385 Marseille, Cedex 05, France.
⁹ Department of Pathology, University of Texas Medical Branch, 301 University Blvd., Route 0428, Galveston, TX 77555-0428, USA.
¹⁰ 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.
¹¹ 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.
¹² 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.
¹³ 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.
¹⁴ 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.

PMID: 27180202
DOI: 10.1016/j.cyto.2016.05.006

Abstract

Background: 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.

Methods: 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.

Results: (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.

Conclusions: 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.

Keywords: CXCL10; IP-10; Inflammation; Mediterranean spotted fever; Rickettsia conorii.

MeSH terms

Adult
Aged
Aged, 80 and over
Boutonneuse Fever / blood*
Boutonneuse Fever / pathology
Chemokine CXCL10 / biosynthesis*
Cohort Studies
Endothelial Cells / metabolism*
Endothelial Cells / pathology
Female
Humans
Male
Middle Aged
Monocytes / metabolism
Monocytes / pathology
Rickettsia conorii*
T-Lymphocytes / metabolism
T-Lymphocytes / pathology

Substances

CXCL10 protein, human
Chemokine CXCL10