title: Roles for phagocytic cells and complement in controlling relapsing fever infection.
abstract: Relapsing fever spirochetes, such as Borrelia hermsii, proliferate to high levels in their hosts' bloodstream until production of IgM against borrelial surface proteins promotes bacterial clearance. The mechanisms by which B. hermsii survives in host blood, as well as the immune mediators that control this infection, remain largely unknown. It has been hypothesized that B. hermsii is naturally resistant to killing by the alternative pathway of complement activation as a result of its ability to bind factor H, a host complement regulator. However, we found that Cfh(-/-) mice were infected to levels identical to those seen in wild-type mice. Moreover, only a small minority of B. hermsii in the blood of wild-type mice had detectable levels of factor H adhered to their outer surfaces. In vitro, complement was found to play a statistically significant role in antibody-mediated inactivation of B. hermsii, although in vivo studies indicated that complement is not essential for host control of B. hermsii. Depletion of mphi and DC from mice had significant impacts on B. hermsii infection, and depleted mice were unable to control bloodstream infections, leading to death. Infection studies using muMT indicated a significant antibody-independent role for mphi and/or DC in host control of relapsing fever infection. Together, these findings indicate mphi and/or DC play a critical role in the production of B. hermsii-specific IgM and for antibody-independent control of spirochete levels.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Woodman
authors.forename: Anne E
authors.initials: AE
authors.lastname: Cooley
authors.forename: Rita
authors.initials: R
authors.lastname: Avdiushko
authors.forename: Amy
authors.initials: A
authors.lastname: Bowman
authors.forename: Marina
authors.initials: M
authors.lastname: Botto
authors.forename: R Mark
authors.initials: RM
authors.lastname: Wooten
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Donald A
authors.initials: DA
authors.lastname: Cohen
authors.forename: Brian
authors.initials: B
authors.lastname: Stevenson
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001898:Borrelia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003167:Complement Activation / Q000276:immunology; D017242:Complement Factor H / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D003433:Crosses, Genetic; D007075:Immunoglobulin M / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism*; D012061:Relapsing Fever / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; D007075:Immunoglobulin M; D017242:Complement Factor H; D003165:Complement System Proteins