title: Early cytokine release in response to live Borrelia burgdorferi Sensu Lato Spirochetes is largely complement independent.
abstract: OBJECTIVE
  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.
authors.affiliation: Linnaeus University Centre for Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Sandholm
authors.affiliation: Department of Clinical Microbiology, Ryhov County Hospital, Jönköping, Sweden; Department of Infection Medicine, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Henningsson
authors.affiliation: Linnaeus University Centre for Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Säve
authors.affiliation: Department of Molecular Biology, University of Umeå, Umeå, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Bergström
authors.affiliation: Department of Infection Medicine, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Pia
authors.initials: P
authors.lastname: Forsberg
authors.affiliation: Linnaeus University Centre for Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden; Division of Clinical Immunology, Rudbeck Laboratory C5, University of Uppsala, Uppsala, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Jonsson
authors.affiliation: Department of Clinical Immunology and Transfusion Medicine, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Ernerudh
authors.affiliation: Linnaeus University Centre for Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden; Division of Clinical Immunology, Rudbeck Laboratory C5, University of Uppsala, Uppsala, Sweden.
authors.forename: Kristina N
authors.initials: KN
authors.lastname: Ekdahl
mesh_terms: D025065:Borrelia burgdorferi / Q000378:metabolism*; D003167:Complement Activation; D003165:Complement System Proteins / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D010587:Phagocytosis
chemical_list: D016207:Cytokines; D003165:Complement System Proteins