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- Sandholm, Kerstin, et al.
(författare)
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Early Cytokine Release in Response to Live Borrelia burgdorferi Sensu Lato Spirochetes Is Largely Complement Independent
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:9, s. e108013-
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Tidskriftsartikel (refereegranskat)abstract
- 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-1 beta, 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.
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| 2. |
- Sandholm, Kerstin, et al.
(författare)
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Early Immune Responses to Borrelia garinii and Borrelia afzeliiin Lyme Borreliosis : Local Complement Activation in Erythema Migrans and in vitro Studies ofComplement Activation, Phagocytosis and Cytokine Profile
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- An optimal eradication of spirochetes in Lyme borreliosis depends on the early immune response, including the potent actions of the complement system. We here assessed possible differences between two Borrelia burgdorferi genospecies in their ability to activate complement, and the consequences of complement activation in terms of phagocytosis and induction of cytokines.Early local complement activation was assessed immunohistochemically in skin biopsies from patients with erythema migrans (EM) caused by B. afzelii or B. garinii. Complement activation, phagocytosis and early cytokine and chemokine release were studied in vitro by incubating clinical isolates of B. afzelii (K78 from a human skin biopsy) and B. garinii (LU59 from human cerebrospinal fluid) in human whole blood.B. afzelii and B. garinii were detected in skin biopsies from EM and deposition of C3-fragments and IgG was found adjacent to the spirochetes. In vitro, B. garinii LU59 induced higher complement activation (measured as the generation of C3a and C5b-9), while B. afzelii K78 recruited more factor H. Phagocytosis by granulocytes and monocytes was demonstrated to be largely dependent on complement activation since phagocytosis was substantially reduced by addition of the C3 inhibitor compstatin or a C5a receptor antagonist. The early cytokine and chemokine release in human blood in response to live spirochetes revealed a rapid and pronounced pro-inflammatory response, mainly associated with the Th1- and Th17-types.We conclude that complement is activated locally in the skin in EM, and that B. garinii LU59 activates complement more than B. afzelii K78. Complement activation is pivotal for efficient phagocytosis of Borrelia spirochetes, especially in early infection before specific antibodies are produced. Both B. garinii LU59 and B. afzelii K78 induce proinflammatory cytokines rapidly, but no clear differences were seen between the two genospecies in this respect.
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