Complement Activation Correlates With Disease Severity and Contributes to Cytokine Responses in Plasmodium falciparum Malaria

Aase Berg; Kari Otterdal; Sam Patel; Miguel Gonca; Catarina David; Ingvild Dalen; Stig Nymo; Margareta Nilsson; Sofia Nordling; Peetra U Magnusson; Thor Ueland; Mauro Prato; Giuliana Giribaldi; Tom Eirik Mollnes; Pål Aukrust; Nina Langeland; Per H Nilsson

doi:10.1093/infdis/jiv283

Complement Activation Correlates With Disease Severity and Contributes to Cytokine Responses in Plasmodium falciparum Malaria

J Infect Dis. 2015 Dec 1;212(11):1835-40. doi: 10.1093/infdis/jiv283. Epub 2015 May 15.

Authors

Aase Berg¹, Kari Otterdal², Sam Patel³, Miguel Gonca³, Catarina David³, Ingvild Dalen⁴, Stig Nymo⁵, Margareta Nilsson⁶, Sofia Nordling⁷, Peetra U Magnusson⁷, Thor Ueland⁸, Mauro Prato⁹, Giuliana Giribaldi¹⁰, Tom Eirik Mollnes¹¹, Pål Aukrust¹², Nina Langeland¹³, Per H Nilsson⁶

Affiliations

¹ Department of Medicine, Stavanger University Hospital Department of Clinical Science, University of Bergen Department of Medicine, Central Hospital of Maputo, Mozambique.
² Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet.
³ Department of Medicine, Central Hospital of Maputo, Mozambique.
⁴ Department of Research, Stavanger University Hospital.
⁵ Department of Immunology, Oslo University Hospital Rikshospitalet Research Laboratory Nordland Hospital, Bodø Faculty of Health Sciences, University of Tromsø, Norway.
⁶ Department of Immunology, Oslo University Hospital Rikshospitalet.
⁷ Department of Immunology, Genetics, and Pathology, the Rudbeck Laboratory, Uppsala University, Sweden.
⁸ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet K. G. Jebsen Inflammatory Research Center, University of Oslo Faculty of Medicine, University of Oslo K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Norway.
⁹ Department of Neuroscience, University of Torino, Italy Department of Public Health and Pediatric Sciences, University of Torino, Italy.
¹⁰ Department of Oncology, University of Torino, Italy.
¹¹ Department of Immunology, Oslo University Hospital Rikshospitalet K. G. Jebsen Inflammatory Research Center, University of Oslo Faculty of Medicine, University of Oslo Research Laboratory Nordland Hospital, Bodø Faculty of Health Sciences, University of Tromsø, Norway.
¹² Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet K. G. Jebsen Inflammatory Research Center, University of Oslo Faculty of Medicine, University of Oslo.
¹³ Department of Clinical Science, University of Bergen Department of Medicine, Haukeland University Hospital, Bergen.

PMID: 25980034
DOI: 10.1093/infdis/jiv283

Abstract

The impact of complement activation and its possible relation to cytokine responses during malaria pathology was investigated in plasma samples from patients with confirmed Plasmodium falciparum malaria and in human whole-blood specimens stimulated with malaria-relevant agents ex vivo. Complement was significantly activated in the malaria cohort, compared with healthy controls, and was positively correlated with disease severity and with certain cytokines, in particular interleukin 8 (IL-8)/CXCL8. This was confirmed in ex vivo-stimulated blood specimens, in which complement inhibition significantly reduced IL-8/CXCL8 release. P. falciparum malaria is associated with systemic complement activation and complement-dependent release of inflammatory cytokines, of which IL-8/CXCL8 is particularly prominent.

Keywords: C5a/C5aR1; IL-8/CXCL8; Plasmodium falciparum; complement activation; cytokines; heme; hemozoin; inflammation; malaria.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Complement Activation / immunology*
Cytokines / metabolism*
Hemeproteins / immunology
Hemin / immunology
Humans
Malaria, Falciparum / epidemiology
Malaria, Falciparum / immunology*
Malaria, Falciparum / metabolism*
Malaria, Falciparum / physiopathology
Plasmodium falciparum / immunology

Substances

Cytokines
Hemeproteins
hemozoin
Hemin