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410          Part tHrEE  Host Defenses to Infectious Agents


        function of key components of the spirochete, could lead to   2.  Krause RM. Metchnikoff and syphilis research during a decade of
        development of single or combination vaccines. Further, the   discovery, 1900-1910. Development of an animal model and a
        identification of host factors that mediate a protective response   preventive treatment set the stage for progress. ASM News
        and those that contribute to inflammation may result in a better   1996;62:307–10.
        understanding of the disease. Overall, the identification of the   3.  Fraser CM, Casjens S, Huang WM, et al. Genomic sequence of
                                                                  a Lyme disease spirochaete, Borrelia burgdorferi. Nature 1997;
        elements that mediate specific tissue tropisms for the bacterium   390:580–6.
        and their interaction with local/infiltrating cellular components   4.  Fraser CM, Norris SJ, Weinstock GM, et al. Complete genome
        can permit the design of targeted therapies in conjunction with   sequence of Treponema pallidum, the syphilis spirochete. Science
        antimicrobial treatments.                                 1998;281:375–88.
           A significant effort is being made to find new antigenic   5.  Anguita J, Hedrick M, Fikrig E. Adaptation of Borrelia burgdorferi
        determinants that can be the base for a vaccine to prevent infection   in the tick and the mammalian host. FEMS Microbiol Rev
        with B. burgdorferi. While the search for spirochetal antigens   2003;27:493–504.
        continue, a new wave of research has focused on finding antigenic   6.  Pal U, Li X, Wang T, et al. TROSPA, an Ixodes scapularis receptor for
        determinants that can prevent the efficient attachment of the   Borrelia burgdorferi. Cell 2004;119:457–68.
        tick vector to the mammalian host, which, in turn, could dampen   7.  Hubner A, Yang X, Nolen DM, et al. Expression of Borrelia burgdorferi
                                                                  OspC and DbpA is controlled by a RpoN-RpoS regulatory pathway. Proc
        the ability of the arthropod to transmit B. burgdorferi and perhaps   Natl Acad Sci USA 2001;98:12724–9.
        other pathogens.                                        8.  Center for Disease Control and Prevention. 2016. Available at: https://
           For syphilis, the study of the microorganism is hampered by   www.cdc.gov/lyme/stats/index.html.
        the difficulties associated with its culture and manipulation.   9.  Guerau-de-Arellano M, Huber BT. Chemokines and Toll-like receptors in
        Although advances have been made in our understanding of the   Lyme disease pathogenesis. Trends Mol Med 2005;11:114–20.
        pathology associated with infection, a significant challenge in   10.  Hawley KL, Olson CM Jr, Iglesias-Pedraz JM, et al. CD14 cooperates with
        the near future is to fully understand this pathogen. An area in   complement receptor 3 to mediate MyD88-independent phagocytosis of
        which advances can be made in the next decade consists of better   Borrelia burgdorferi. Proc Natl Acad Sci USA 2012;109:1228–32.
        education of populations that are at risk of acquiring the infection.   11.  Lawrenz MB, Wooten RM, Zachary JF, et al. Effect of complement
        Because these populations are usually associated with low-income   component C3 deficiency on experimental Lyme borreliosis in mice.
                                                                  Infect Immun 2003;71:4432–40.
        communities, a significant investment needs to be made to enable   12.  Kochi SK, Johnson RC. Role of immunoglobulin G in killing of Borrelia
        persons at risk to better evade the transmission of the pathogen,   burgdorferi by the classical complement pathway. Infect Immun
        through education, better diagnostics, and rapid antimicrobial   1988;56:314–21.
        treatment.                                             13.  Madar M, Bencurova E, Mlynarcik P, et al. Exploitation of complement
                                                                  regulatory proteins by Borrelia and Francisella. Mol Biosyst
                                                                  2015;11:1684–95.
        CONCLUSIONS                                            14.  Pausa M, Pellis V, Cinco M, et al. Serum-resistant strains of Borrelia
        Spirochetes are a phylogenetically ancient and distinct group     burgdorferi evade complement-mediated killing by expressing a CD59-like
        of microorganisms. Because of their propensity to cause    complement inhibitory molecule. J Immunol 2003;170:3214–22.
        diseases in humans,  B. burgdorferi and  T. pallidum are the    15.  Hovis KM, McDowell JV, Griffin L, et al. Identification and
                                                                  characterization of a linear-plasmid-encoded factor H-binding protein
        two most-well-studied spirochetes. However, the inability to   (FhbA) of the relapsing fever spirochete Borrelia hermsii. J Bacteriol
        culture T. pallidum in vitro has made researching this spirochete   2004;186:2612–18.
        very  difficult,  and  as  a  consequence,  the  immune  response    16.  Garcia BL, Zhi H, Wager B, et al. Borrelia burgdorferi BBK32 inhibits the
        that follows infection with this spirochete remains poorly   classical pathway by blocking activation of the C1 complement complex.
        understood.                                               PLoS Pathog 2016;12:e1005404.
           The etiological agents of Lyme disease and syphilis are similar   17.  Gross DM, Steere AC, Huber BT. T helper 1 response is dominant and
        in that they have relatively small genomes, surviving only in   localized to the synovial fluid in patients with Lyme arthritis. J Immunol
        association with a host and eliciting inflammatory disease, but   1998;160:1022–8.
        genomic comparison clearly shows that  T. pallidum and  B.   18.  Zhang JR, Hardham JM, Barbour AG, et al. Antigenic variation in Lyme
        burgdorferi are not closely related. It seems likely that despite   disease borreliae by promiscuous recombination of VMP-like sequence
                                                                  cassettes. Cell 1997;89:275–85.
        some similarities, these spirochetes evolved independently from   19.  Ramamoorthi N, Narasimhan S, Pal U, et al. The Lyme disease agent
        a more complex ancestor, resulting in differences in their life-  exploits a tick protein to infect the mammalian host. Nature
        cycles, environmental adaptations, and the pathology associated   2005;436:573–7.
        with their infection. Therefore it is not surprising to learn of   20.  Cox DL, Chang P, McDowall AW, et al. The outer membrane, not a coat
        the differences in the host immune responses to B. burgdorferi   of host proteins, limits antigenicity of virulent Treponema pallidum.
        and T. pallidum. Both the host response to these spirochetes and   Infect Immun 1992;60:1076–83.
        their infectivity determine the extent of pathology following   21.  Salazar JC, Hazlett KR, Radolf JD. The immune response to infection
        infection.                                                with Treponema pallidum, the stealth pathogen. Microbes Infect
                                                                  2002;4:1133–40.
                                                               22.  Salazar JC, Cruz AR, Pope CD, et al. Treponema pallidum elicits innate
        Please check your eBook at https://expertconsult.inkling.com/   and adaptive cellular immune responses in skin and blood during
        for self-assessment questions. See inside cover for registration   secondary syphilis: a flow-cytometric analysis. J Infect Dis
        details.                                                  2007;195:879–87.
                                                               23.  Blanco DR, Champion CI, Lewinski MA, et al. Immunization with
        REFERENCES                                                Treponema pallidum outer membrane vesicles induces high-titer
                                                                  complement-dependent treponemicidal activity and aggregation of T.
         1.  Burgdorfer W, Barbour AG, Hayes SF, et al. Lyme disease-a tick-borne   pallidum rare outer membrane proteins (TROMPs). J Immunol
           spirochetosis? Science 1982;216:1317–19.               1999;163(5):2741–6.
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