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A Novel Animal Model of Borrelia recurrentis Louse-Borne Relapsing Fever Borreliosis Using Immunodeficient Mice

DOI: 10.1371/journal.pntd.0000522

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Abstract:

Louse-borne relapsing fever (LBRF) borreliosis is caused by Borrelia recurrentis, and it is a deadly although treatable disease that is endemic in the Horn of Africa but has epidemic potential. Research on LBRF has been severely hampered because successful infection with B. recurrentis has been achieved only in primates (i.e., not in other laboratory or domestic animals). Here, we present the first non-primate animal model of LBRF, using SCID (-B, -T cells) and SCID BEIGE (-B, -T, -NK cells) immunocompromised mice. These animals were infected with B. recurrentis A11 or A17, or with B. duttonii 1120K3 as controls. B. recurrentis caused a relatively mild but persistent infection in SCID and SCID BEIGE mice, but did not proliferate in NUDE (-T) and BALB/c (wild-type) mice. B. duttonii was infectious but not lethal in all animals. These findings demonstrate that the immune response can limit relapsing fever even in the absence of humoral defense mechanisms. To study the significance of phagocytic cells in this context, we induced systemic depletion of such cells in the experimental mice by injecting them with clodronate liposomes, which resulted in uncontrolled B. duttonii growth and a one-hundred-fold increase in B. recurrentis titers in blood. This observation highlights the role of macrophages and other phagocytes in controlling relapsing fever infection. B. recurrentis evolved from B. duttonii to become a primate-specific pathogen that has lost the ability to infect immunocompetent rodents, probably through genetic degeneration. Here, we describe a novel animal model of B. recurrentis based on B- and T-cell-deficient mice, which we believe will be very valuable in future research on LBRF. Our study also reveals the importance of B-cells and phagocytes in controlling relapsing fever infection.

References

[1]  Bryceson AD, Parry EH, Perine PL, Warrell DA, Vukotich D, et al. (1970) Louse-borne relapsing fever. Q J Med 39: 129–170.
[2]  Felsenfeld O (1971) Borrelia: Strains, Vectors, Human and Animal Borreliosis. St Louis, MO: Green. 1971.
[3]  Ramos JM, Malmierca E, Reyes F, Tesfamariam A (2009) Louse-borne relapsing fever in Ethiopian children: experience of a rural hospital. Trop Doct 39: 34–36. doi: 10.1258/td.2008.080157
[4]  Abdalla RE (1969) Some studies on relapsing fever in the Sudan. J Trop Med Hyg 72: 125–128.
[5]  de Jong J, Wilkinson RJ, Schaeffers P, Sondorp HE, Davidson RN (1995) Louse-borne relapsing fever in southern Sudan. Trans R Soc Trop Med Hyg 89: 621. doi: 10.1016/0035-9203(95)90414-X
[6]  Ramos JM, Malmierca E, Reyes F, Tesfamariam A (2008) Results of a 10-year survey of louse-borne relapsing fever in southern Ethiopia: a decline in endemicity. Ann Trop Med Parasitol 102: 467–469. doi: 10.1179/136485908X300887
[7]  Cutler SJ (2006) Possibilities for relapsing fever reemergence. Emerg Infect Dis. [serial on the Internet] Mar. Available at: http://www.cdc.gov/ncidod/EID/vol12no03/?05-0899.htm.
[8]  Raoult D, Roux V (1999) The body louse as a vector of reemerging human diseases. Clin Infect Dis 29: 888–911. doi: 10.1086/520454
[9]  Lescot M, Audic S, Robert C, Nguyen TT, Blanc G, et al. (2008) The genome of Borrelia recurrentis, the agent of deadly louse-borne relapsing fever, is a degraded subset of tick-borne Borrelia duttonii. PLoS Genet 4: e1000185. doi:10.1371/journal.pgen.1000185.
[10]  Judge DM, La Croix JT, Perine PL (1974) Experimental louse-borne relapsing fever in the grivet monkey, Cercopithecus aethiops. I. Clinical course. AmJ Trop Med Hyg 23: 957–961.
[11]  Cutler SJ, Fekade D, Hussein K, Knox KA, Melka A, et al. (1994) Successful in-vitro cultivation of Borrelia recurrentis. Lancet 343: 242. doi: 10.1016/S0140-6736(94)91032-4
[12]  Bosma GC, Custer RP, Bosma MJ (1983) A severe combined immunodeficiency mutation in the mouse. Nature 301: 527–530. doi: 10.1038/301527a0
[13]  Flanagan SP (1966) ‘Nude’, a new hairless gene with pleiotropic effects in the mouse. Genet Res 8: 295–309. doi: 10.1017/S0016672300010168
[14]  Perou CM, Moore KJ, Nagle DL, Misumi DJ, Woolf EA, et al. (1996) Identification of the murine beige gene by YAC complementation and positional cloning. Nat Genet 13: 303–308. doi: 10.1038/ng0796-303
[15]  Cote CK, Rea KM, Norris SL, van Rooijen N, Welkos SL (2004) The use of a model of in vivo macrophage depletion to study the role of macrophages during infection with Bacillus anthracis spores. Microb Pathog 37: 169–175. doi: 10.1016/j.micpath.2004.06.013
[16]  Kaparakis M, Walduck AK, Price JD, Pedersen JS, van Rooijen N, et al. (2008) Macrophages are mediators of gastritis in acute Helicobacter pylori infection in C57BL/6 mice. Infect Immun 76: 2235–2239. doi: 10.1128/IAI.01481-07
[17]  Samsom JN, Annema A, Groeneveld PH, van Rooijen N, Langermans JA, et al. (1997) Elimination of resident macrophages from the livers and spleens of immune mice impairs acquired resistance against a secondary Listeria monocytogenes infection. Infect Immun 65: 986–993.
[18]  Van Andel RA, Hook RR Jr, Franklin CL, Besch-Williford CL, van Rooijen N, et al. (1997) Effects of neutrophil, natural killer cell, and macrophage depletion on murine Clostridium piliforme infection. Infect Immun 65: 2725–2731.
[19]  Van Rooijen N, Sanders A (1994) Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods 174: 83–93. doi: 10.1016/0022-1759(94)90012-4
[20]  Buiting AM, Zhou F, Bakker JA, van Rooijen N, Huang L (1996) Biodistribution of clodronate and liposomes used in the liposome mediated macrophage ‘suicide’ approach. J Immunol Methods 192: 55–62. doi: 10.1016/0022-1759(96)00034-8
[21]  Larsson C, Lundqvist J, Bergstrom S (2008) Residual brain infection in murine relapsing fever borreliosis can be successfully treated with ceftriaxone. Microb Pathog 44: 262–264. doi: 10.1016/j.micpath.2007.11.002
[22]  Larsson C, Andersson M, Guo BP, Nordstrand A, Hagerstrand I, et al. (2006) Complications of pregnancy and transplacental transmission of relapsing-fever borreliosis. J Infect Dis 194: 1367–1374. doi: 10.1086/508425
[23]  Barbour AG (1984) Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med 57: 521–525.
[24]  Larsson C, Andersson M, Pelkonen J, Guo BP, Nordstrand A, et al. (2006) Persistent brain infection and disease reactivation in relapsing fever borreliosis. Microbes Infect 8: 2213–2219. doi: 10.1016/j.micinf.2006.04.007
[25]  Lopez JE, Schrumpf ME, Raffel SJ, Policastro PF, Porcella SF, et al. (2008) Relapsing fever spirochetes retain infectivity after prolonged in vitro cultivation. Vector Borne Zoonotic Dis 8: 813–820. doi: 10.1089/vbz.2008.0033
[26]  Malkiel S, Kuhlow CJ, Mena P, Benach JL (2009) The loss and gain of marginal zone and peritoneal B cells is different in response to relapsing fever and Lyme disease Borrelia. J Immunol 182: 498–506.
[27]  Connolly SE, Benach JL (2001) Cutting edge: the spirochetemia of murine relapsing fever is cleared by complement-independent bactericidal antibodies. J Immunol 167: 3029–3032.
[28]  Newman K Jr, Johnson RC (1981) In vivo evidence that an intact lytic complement pathway is not essential for successful removal of circulating Borrelia turicatae from mouse blood. Infect Immun 31: 465–469.
[29]  McKisic MD, Barthold SW (2000) T-cell-independent responses to Borrelia burgdorferi are critical for protective immunity and resolution of lyme disease. Infect Immun 68: 5190–5197. doi: 10.1128/IAI.68.9.5190-5197.2000
[30]  Londono D, Marques A, Hornung RL, Cadavid D (2008) IL-10 helps control pathogen load during high-level bacteremia. J Immunol 181: 2076–2083.
[31]  Meri T, Cutler SJ, Blom AM, Meri S, Jokiranta TS (2006) Relapsing fever spirochetes Borrelia recurrentis and B. duttonii acquire complement regulators C4b-binding protein and factor H. Infect Immun 74: 4157–4163. doi: 10.1128/IAI.00007-06
[32]  Grosskinsky S, Schott M, Brenner C, Cutler SJ, Kraiczy P, et al. (2009) Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity. PLoS ONE 4: e4858. doi: 10.1371/journal.pone.0004858
[33]  McCall PJ, Hume JC, Motshegwa K, Pignatelli P, Talbert A, et al. (2007) Does tick-borne relapsing fever have an animal reservoir in East Africa? Vector Borne Zoonotic Dis 7: 659–666. doi: 10.1089/vbz.2007.0151
[34]  Blanc G, Ogata H, Robert C, Audic S, Suhre K, et al. (2007) Reductive genome evolution from the mother of Rickettsia. PLoS Genet 3: e14. doi:10.1371/journal.pgen.0030014.
[35]  Davis PH, Stanley SL Jr (2003) Breaking the species barrier: use of SCID mouse-human chimeras for the study of human infectious diseases. Cell Microbiol 5: 849–860. doi: 10.1046/j.1462-5822.2003.00321.x
[36]  Vidal V, Scragg IG, Cutler SJ, Rockett KA, Fekade D, et al. (1998) Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever. Nat Med 4: 1416–1420. doi: 10.1038/4007
[37]  Battisti JM, Raffel SJ, Schwan TG (2008) A system for site-specific genetic manipulation of the relapsing fever spirochete Borrelia hermsii. Methods Mol Biol 431: 69–84.

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