@article{45880bf379334434a0615808bb477311,
title = "CD55 Facilitates Immune Evasion by Borrelia crocidurae, an Agent of Relapsing Fever",
abstract = "Relapsing fever, caused by diverse Borrelia spirochetes, is prevalent in many parts of the world and causes significant morbidity and mortality. To investigate the pathoetiology of relapsing fever, we performed a high-throughput screen of Borrelia-binding host factors using a library of human extracellular and secretory proteins and identified CD55 as a novel host binding partner of Borrelia crocidurae and Borrelia persica, two agents of relapsing fever in Africa and Eurasia. CD55 is present on the surface of erythrocytes, carries the Cromer blood group antigens, and protects cells from complement-mediated lysis. Using flow cytometry, we confirmed that both human and murine CD55 bound to B. crocidurae and B. persica. Given the expression of CD55 on erythrocytes, we investigated the role of CD55 in pathological B. crocidurae-induced erythrocyte aggregation (rosettes), which enables spirochete immune evasion. We showed that rosette formation was partially dependent on host cell CD55 expression. Pharmacologically, soluble recombinant CD55 inhibited erythrocyte rosette formation. Finally, CD55-deficient mice infected with B. crocidurae had a lower pathogen load and elevated proinflammatory cytokine and complement factor C5a levels. In summary, our results indicate that CD55 is a host factor that is manipulated by the causative agents of relapsing fever for immune evasion.",
keywords = "host response, host-pathogen interactions, immunopathogenesis, relapsing fever",
author = "Gunjan Arora and Lynn, {Geoffrey E.} and Xiaotian Tang and Rosen, {Connor E.} and Dieuwertje Hoornstra and Andaleeb Sajid and Hovius, {Joppe W.} and Palm, {Noah W.} and Ring, {Aaron M.} and Erol Fikrig",
note = "Funding Information: This work was supported by grants from the NIH (grants number AI126033, AI138949, and AI157014) and the Steven and Alexandra Cohen Foundation to Erol Fikrig. This work was also supported by ZonMW as part of the project Ticking on Pandora{\textquoteright}s Box, a study into tick-borne pathogens in Europe (project no. 522003007), to Dieuwertje Hoornstra and Joppe W. Hovius. Funding Information: We thank Alan Barbour for helpful advice in the project. We thank Jiri Cerny, Akash Gupta, Maryna Golovchenko, Natalie Rudenko, and Ulrike Munderloh for help with the BASEHIT screen. We acknowledge Wenchao Song (University of Pennsylvania) for providing CD55 (DAF) knockout mice. We acknowledge Jun Liu and Chunyan Wang for their help in structural studies. We also thank Alje van Dam, Amsterdam UMC, for providing B. crocidurae and Sven Bergstr{\"o}m and Guy Baranton from Pasteur Institute Paris for B. persica strains. This work was supported by grants from the NIH (grants number AI126033, AI138949, and AI157014) and the Steven and Alexandra Cohen Foundation to Erol Fikrig. This work was also supported by ZonMW as part of the project Ticking on Pandora{\textquoteright}s Box, a study into tick-borne pathogens in Europe (project no. 522003007), to Dieuwertje Hoornstra and Joppe W. Hovius. Publisher Copyright: Copyright {\textcopyright} 2022 Arora et al.",
year = "2022",
month = sep,
doi = "https://doi.org/10.1128/mbio.01161-22",
language = "English",
volume = "13",
pages = "e0116122",
journal = "MBio",
issn = "2161-2129",
publisher = "American Society for Microbiology",
number = "5",
}