Immunological responses to the relapsing fever spirochete borrelia turicatae in infected rhesus macaques: Implications for pathogenesis and diagnosis

Monica E. Embers, Aparna Krishnavajhala, Brittany A. Armstrong, Michael W. Curtis, Bapi Pahar, Hannah K. Wilder, Michael S. Allen, Paul A. Beare, Nicole R. Hasenkampf, Job E. Lopez

Research output: Contribution to journalArticle

Abstract

The global public health impact of relapsing fever (RF) spirochetosis is significant, since the pathogens exist on five of seven continents. The hallmark sign of infection is episodic fever and the greatest threat is to the unborn. With the goal of better understanding the specificity of B-cell responses and the role of immune responses in pathogenicity, we infected rhesus macaques with Borrelia turicatae (a new world RF spirochete species) by tick bite and monitored the immune responses generated in response to the pathogen. Specifically, we evaluated inflammatory mediator induction by the pathogen, host antibody responses to specific antigens, and peripheral lymphocyte population dynamics. Our results indicate that B. turicatae elicits from peripheral blood cells key inflammatory response mediators (interleukin-1 and tumor necrosis factor alpha), which are associated with preterm abortion. Moreover, a global decline in peripheral B-cell populations was observed in all animals at 14 days postinfection. Serological responses were also evaluated to assess the antigenicity of three surface proteins: BipA, BrpA, and Bta112. Interestingly, a distinction was observed between antibodies generated in nonhuman primates and mice. Our results provide support for the nonhuman primate model not only in studies of prenatal pathogenesis but also for diagnostic and vaccine antigen identification and testing.

Original languageEnglish
Article numbere00900
JournalInfection and Immunity
Volume87
Issue number4
DOIs
StatePublished - 1 Apr 2019

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Relapsing Fever
Borrelia
Spirochaetales
Macaca mulatta
Primates
B-Lymphocytes
Tick Bites
Antigens
Population Dynamics
Interleukin-1
Antibody Formation
Virulence
Blood Cells
Membrane Proteins
Fever
Vaccines
Public Health
Tumor Necrosis Factor-alpha
Lymphocytes
Antibodies

Keywords

  • Adaptive immunity
  • Borrelia
  • Humoral immunity
  • Nonhuman primate
  • Relapsing fever

Cite this

Embers, M. E., Krishnavajhala, A., Armstrong, B. A., Curtis, M. W., Pahar, B., Wilder, H. K., ... Lopez, J. E. (2019). Immunological responses to the relapsing fever spirochete borrelia turicatae in infected rhesus macaques: Implications for pathogenesis and diagnosis. Infection and Immunity, 87(4), [e00900]. https://doi.org/10.1128/IAI.00900-18
Embers, Monica E. ; Krishnavajhala, Aparna ; Armstrong, Brittany A. ; Curtis, Michael W. ; Pahar, Bapi ; Wilder, Hannah K. ; Allen, Michael S. ; Beare, Paul A. ; Hasenkampf, Nicole R. ; Lopez, Job E. / Immunological responses to the relapsing fever spirochete borrelia turicatae in infected rhesus macaques : Implications for pathogenesis and diagnosis. In: Infection and Immunity. 2019 ; Vol. 87, No. 4.
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abstract = "The global public health impact of relapsing fever (RF) spirochetosis is significant, since the pathogens exist on five of seven continents. The hallmark sign of infection is episodic fever and the greatest threat is to the unborn. With the goal of better understanding the specificity of B-cell responses and the role of immune responses in pathogenicity, we infected rhesus macaques with Borrelia turicatae (a new world RF spirochete species) by tick bite and monitored the immune responses generated in response to the pathogen. Specifically, we evaluated inflammatory mediator induction by the pathogen, host antibody responses to specific antigens, and peripheral lymphocyte population dynamics. Our results indicate that B. turicatae elicits from peripheral blood cells key inflammatory response mediators (interleukin-1 and tumor necrosis factor alpha), which are associated with preterm abortion. Moreover, a global decline in peripheral B-cell populations was observed in all animals at 14 days postinfection. Serological responses were also evaluated to assess the antigenicity of three surface proteins: BipA, BrpA, and Bta112. Interestingly, a distinction was observed between antibodies generated in nonhuman primates and mice. Our results provide support for the nonhuman primate model not only in studies of prenatal pathogenesis but also for diagnostic and vaccine antigen identification and testing.",
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Embers, ME, Krishnavajhala, A, Armstrong, BA, Curtis, MW, Pahar, B, Wilder, HK, Allen, MS, Beare, PA, Hasenkampf, NR & Lopez, JE 2019, 'Immunological responses to the relapsing fever spirochete borrelia turicatae in infected rhesus macaques: Implications for pathogenesis and diagnosis', Infection and Immunity, vol. 87, no. 4, e00900. https://doi.org/10.1128/IAI.00900-18

Immunological responses to the relapsing fever spirochete borrelia turicatae in infected rhesus macaques : Implications for pathogenesis and diagnosis. / Embers, Monica E.; Krishnavajhala, Aparna; Armstrong, Brittany A.; Curtis, Michael W.; Pahar, Bapi; Wilder, Hannah K.; Allen, Michael S.; Beare, Paul A.; Hasenkampf, Nicole R.; Lopez, Job E.

In: Infection and Immunity, Vol. 87, No. 4, e00900, 01.04.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Immunological responses to the relapsing fever spirochete borrelia turicatae in infected rhesus macaques

T2 - Implications for pathogenesis and diagnosis

AU - Embers, Monica E.

AU - Krishnavajhala, Aparna

AU - Armstrong, Brittany A.

AU - Curtis, Michael W.

AU - Pahar, Bapi

AU - Wilder, Hannah K.

AU - Allen, Michael S.

AU - Beare, Paul A.

AU - Hasenkampf, Nicole R.

AU - Lopez, Job E.

PY - 2019/4/1

Y1 - 2019/4/1

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