title: There Is a Method to the Madness: Strategies to Study Host Complement Evasion by Lyme Disease and Relapsing Fever Spirochetes.
abstract: Lyme disease and relapsing fever are caused by variousBorreliaspecies. Lyme diseaseborreliae, the most common vector-borne pathogens in both the U.S. and Europe, are transmitted byIxodesticks and disseminate from the site of tick bites to tissues leading to erythema migrans skin rash, arthritis, carditis, and neuroborreliosis. Relapsing feverborreliae, carried by ticks and lice, trigger reoccurring fever episodes. Following transmission, spirochetes survive in the blood to induce bacteremia at the early stages of infection, which is thought to promote evasion of the host complement system. The complement system acts as an important innate immune defense mechanism in humans and vertebrates. Upon activation, the cleaved complement components form complexes on the pathogen surface to eventually promote bacteriolysis. The complement system is negatively modulated by a number of functionally diverse regulators to avoid tissue damage. To evade and inhibit the complement system, spirochetes are capable of binding complement components and regulators. Complement inhibition results in bacterial survival in serum (serum resistance) and is thought to promote bloodstream survival, which facilitates spirochete dissemination and disease manifestations. In this review, we discuss current methodologies to elucidate the mechanisms ofBorreliaspp. that promote serum resistance and bloodstream survival, as well as novel methods to study factors responsible for bloodstream survival of Lyme diseaseborreliaethat can be applied to relapsing feverborreliae. Understanding the mechanisms these pathogens utilize to evade the complement system will ultimately aid in the development of novel therapeutic strategies and disease prevention to improve human health.
authors.affiliation: Division of Infectious Disease, Wadsworth Center, New York State Department of Health Albany, NY, USA.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Marcinkiewicz
authors.affiliation: Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt am Main Frankfurt am Main, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraiczy
authors.affiliation: Division of Infectious Disease, Wadsworth Center, New York State Department of Health Albany, NY, USA.
authors.forename: Yi-Pin
authors.initials: YP
authors.lastname: Lin
keywords: Lyme disease; blood stream survival; borrelia; complement system; innate immunity; relapsing fever; spirochetes