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.
N1 - Funding Information:
Funding for this work was provided by a TNPRC pilot grant (M.E.E. and J.E.L.), NIH grants AI091652 and AI103724 (J.E.L.), and the TNPRC base grant (NIH) 5 P51 OD 011104-56.
Publisher Copyright:
Copyright © 2019 American Society for Microbiology. All Rights Reserved.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
KW - Adaptive immunity
KW - Borrelia
KW - Humoral immunity
KW - Nonhuman primate
KW - Relapsing fever
UR - http://www.scopus.com/inward/record.url?scp=85063713135&partnerID=8YFLogxK
U2 - 10.1128/IAI.00900-18
DO - 10.1128/IAI.00900-18
M3 - Article
C2 - 30642902
AN - SCOPUS:85063713135
SN - 0019-9567
VL - 87
JO - Infection and Immunity
JF - Infection and Immunity
IS - 4
M1 - e00900
ER -