Infection with Borrelia spirochaetes leads to the launch of specific and non‐specific immunological response in humans. Activation of the complement system is one of the first defence mechanisms against penetrating pathogens. The aim of this study was to select genes related to the alternative pathway of the complement system [including complement factor H (CFH)], differentiating the type of infection in the system model, that is, a culture of normal human diploid fibroblasts infected with three different spirochaete genospecies: Borrelia afzelii, Borrelia garinii and Borrelia burgdorferii sensu stricto, by comparing the infected fibroblast culture with the control fibroblast one. With the use of oligonucleotide microarrays HGU‐133A, the differences in the expression of genes selected on the basis of a scientific database Affymetrix were studied by comparing transcriptomes from the four cultures of fibroblasts. In the result of infection of fibroblast cultivation with a specific Borrelia genospecies, a variable expression of certain CFH and complement system‐associated genes, specific for one genospecies only, B. afzelii– C1QBP, CD59, C2, CD46 and FHL1; B. garinii – C1S and CLU; Borrelia burgeforii– CFB, A2M and VSIG4, was observed. CFH differentiates infections induced by B. afzelii and B. garinii from infections induced by B. burgdorferii sensu stricto.
Complement factor H (CFH) is one of the most important negative regulators of the alternative pathway of the complement system. It is a glycoprotein belonging to the protein H family, which is synthesized mainly in the liver and is composed into a globular protein consisting of 60 amino acid domains in the serum. It shows specificity for C3b molecule of the complement system present in the serum or bound to the cell surface. It inhibits the steady formation of C3 convertase enzymes and the binding of C2 to C4b and factor B to C3b. It accelerates the decomposition of C2a into C4b and the displacement of Bb from C3b. The present paper discusses the composition, properties and functions of the complement factor and the family it belongs to. The paper focuses in particular on its role in the pathogenesis of an infection caused by the spirochetes of the Borrelia genus. Through binding CFH and other related proteins, bacteria of the Borrelia species inhibit the key effect of the alternative pathway of the complement system - the lysis of spirochete cells dependent on the complement's activation. The mechanism enables pathogens to spread in the host organism and facilitates the evolution of the disease. Discovering the immune mechanisms of the infection caused by the spirochetes of the Borrelia genus may allow for implementing a therapy blocking the binding of complement factor H early enough, apart from the standard treatment of the disease.
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