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 Olano, Camilla Schjalm, Bente Halvorsen, José A. Oteo, Tom Eirik Mollnes, Pål Aukrust, Per H. Nilsson

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)269-274
Number of pages6
JournalCytokine
Volume83
DOIs
StatePublished - Jul 1 2016

Fingerprint

Rickettsia Infections
Rickettsia conorii
Endothelial cells
Blood
Endothelial Cells
Chemical activation
T-cells
Serum
Macrophages
Infiltration
Cytokines
T-Lymphocytes
Interferons
Muscle
Assays
Bacteria
Cells
Plasmas
Recovery
Smooth Muscle Myocytes

Keywords

  • CXCL10
  • Inflammation
  • IP-10
  • Mediterranean spotted fever
  • Rickettsia conorii

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

Cite this

Otterdal, K., Portillo, A., Astrup, E., Ludviksen, J., Davì, G., Holm, S., ... Nilsson, P. H. (2016). High serum CXCL10 in Rickettsia conorii infection is endothelial cell mediated subsequent to whole blood activation. Cytokine, 83, 269-274. https://doi.org/10.1016/j.cyto.2016.05.006

High serum CXCL10 in Rickettsia conorii infection is endothelial cell mediated subsequent to whole blood activation. / Otterdal, Kari; Portillo, Aránzazu; Astrup, Elisabeth; Ludviksen, Judith; Davì, Giovanni; Holm, Sverre; Santilli, Francesca; Vitale, Giustina; Raoult, Didier; Olano, Juan; Schjalm, Camilla; Halvorsen, Bente; Oteo, José A.; Mollnes, Tom Eirik; Aukrust, Pål; Nilsson, Per H.

In: Cytokine, Vol. 83, 01.07.2016, p. 269-274.

Research output: Contribution to journalArticle

Otterdal, K, Portillo, A, Astrup, E, Ludviksen, J, Davì, G, Holm, S, Santilli, F, Vitale, G, Raoult, D, Olano, J, Schjalm, C, Halvorsen, B, Oteo, JA, Mollnes, TE, Aukrust, P & Nilsson, PH 2016, 'High serum CXCL10 in Rickettsia conorii infection is endothelial cell mediated subsequent to whole blood activation', Cytokine, vol. 83, pp. 269-274. https://doi.org/10.1016/j.cyto.2016.05.006
Otterdal, Kari ; Portillo, Aránzazu ; Astrup, Elisabeth ; Ludviksen, Judith ; Davì, Giovanni ; Holm, Sverre ; Santilli, Francesca ; Vitale, Giustina ; Raoult, Didier ; Olano, Juan ; Schjalm, Camilla ; Halvorsen, Bente ; Oteo, José A. ; Mollnes, Tom Eirik ; Aukrust, Pål ; Nilsson, Per H. / High serum CXCL10 in Rickettsia conorii infection is endothelial cell mediated subsequent to whole blood activation. In: Cytokine. 2016 ; Vol. 83. pp. 269-274.
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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.",
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T1 - High serum CXCL10 in Rickettsia conorii infection is endothelial cell mediated subsequent to whole blood activation

AU - Otterdal, Kari

AU - Portillo, Aránzazu

AU - Astrup, Elisabeth

AU - Ludviksen, Judith

AU - Davì, Giovanni

AU - Holm, Sverre

AU - Santilli, Francesca

AU - Vitale, Giustina

AU - Raoult, Didier

AU - Olano, Juan

AU - Schjalm, Camilla

AU - Halvorsen, Bente

AU - Oteo, José A.

AU - Mollnes, Tom Eirik

AU - Aukrust, Pål

AU - Nilsson, Per H.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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.

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KW - Rickettsia conorii

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