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Early cytokine release in response to live Borrelia burgdorferi Sensu Lato Spirochetes is largely complement independent
Linneaues University, Kalmar .
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Ryhov County Hospital Jönköping .
Linneaues University, Kalmar.
University of Umeå .
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2014 (English)In: PloS one, ISSN 1932-6203, Vol. 9, no 9, e108013- p.Article in journal (Refereed) Published
Abstract [en]

AIM: Here we investigated the role of complement activation in phagocytosis and the release of cytokines and chemokines in response to two clinical isolates: Borrelia afzelii K78, which is resistant to complement-mediated lysis, and Borrelia garinii LU59, which is complement-sensitive.

METHODS: Borrelia spirochetes were incubated in hirudin plasma, or hirudin-anticoagulated whole blood. Complement activation was measured as the generation of C3a and sC5b-9. Binding of the complement components C3, factor H, C4, and C4BP to the bacterial surfaces was analyzed. The importance of complement activation on phagocytosis, and on the release of cytokines and chemokines, was investigated using inhibitors acting at different levels of the complement cascade.

RESULTS: 1) Borrelia garinii LU59 induced significantly higher complement activation than did Borrelia afzelii K78. 2) Borrelia afzelii K78 recruited higher amounts of factor H resulting in significantly lower C3 binding. 3) Both Borrelia strains were efficiently phagocytized by granulocytes and monocytes, with substantial inhibition by complement blockade at the levels of C3 and C5. 4) The release of the pro-inflammatory cytokines and chemokines IL-1β, IL-6, TNF, CCL20, and CXCL8, together with the anti-inflammatory IL-10, were increased the most (by>10-fold after exposure to Borrelia). 5) Both strains induced a similar release of cytokines and chemokines, which in contrast to the phagocytosis, was almost totally unaffected by complement blockade.

CONCLUSIONS: Our results show that complement activation plays an important role in the process of phagocytosis but not in the subsequent cytokine release in response to live Borrelia spirochetes.

Place, publisher, year, edition, pages
Public Library of Science , 2014. Vol. 9, no 9, e108013- p.
National Category
Infectious Medicine
URN: urn:nbn:se:liu:diva-112749DOI: 10.1371/journal.pone.0108013ISI: 000345745400038PubMedID: 25265036OAI: diva2:771018
Available from: 2014-12-12 Created: 2014-12-12 Last updated: 2015-10-09

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Henningsson, Anna JForsberg, PiaErnerudh, Jan
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Division of Microbiology and Molecular MedicineFaculty of Health SciencesDepartment of Infectious DiseasesDivision of Inflammation MedicineDepartment of Clinical Immunology and Transfusion Medicine
Infectious Medicine

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