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Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection.
PLoS Pathog. 2015 Jul; 11(7):e1004976.PP

Abstract

Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host's ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long-term immunity to this emerging disease threat.

Authors+Show Affiliations

Center for Comparative Medicine, University of California, Davis, Davis, California, United States of America; Microbiology Graduate Group, University of California, Davis, Davis, California, United States of America.Center for Comparative Medicine, University of California, Davis, Davis, California, United States of America; Microbiology Graduate Group, University of California, Davis, Davis, California, United States of America.Center for Comparative Medicine, University of California, Davis, Davis, California, United States of America.Center for Comparative Medicine, University of California, Davis, Davis, California, United States of America; Microbiology Graduate Group, University of California, Davis, Davis, California, United States of America; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26136236

Citation

Elsner, Rebecca A., et al. "Suppression of Long-Lived Humoral Immunity Following Borrelia Burgdorferi Infection." PLoS Pathogens, vol. 11, no. 7, 2015, pp. e1004976.
Elsner RA, Hastey CJ, Olsen KJ, et al. Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection. PLoS Pathog. 2015;11(7):e1004976.
Elsner, R. A., Hastey, C. J., Olsen, K. J., & Baumgarth, N. (2015). Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection. PLoS Pathogens, 11(7), e1004976. https://doi.org/10.1371/journal.ppat.1004976
Elsner RA, et al. Suppression of Long-Lived Humoral Immunity Following Borrelia Burgdorferi Infection. PLoS Pathog. 2015;11(7):e1004976. PubMed PMID: 26136236.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection. AU - Elsner,Rebecca A, AU - Hastey,Christine J, AU - Olsen,Kimberly J, AU - Baumgarth,Nicole, Y1 - 2015/07/02/ PY - 2014/09/22/received PY - 2015/05/26/accepted PY - 2015/7/3/entrez PY - 2015/7/3/pubmed PY - 2016/4/5/medline SP - e1004976 EP - e1004976 JF - PLoS pathogens JO - PLoS Pathog. VL - 11 IS - 7 N2 - Lyme Disease caused by infection with Borrelia burgdorferi is an emerging infectious disease and already by far the most common vector-borne disease in the U.S. Similar to many other infections, infection with B. burgdorferi results in strong antibody response induction, which can be used clinically as a diagnostic measure of prior exposure. However, clinical studies have shown a sometimes-precipitous decline of such antibodies shortly following antibiotic treatment, revealing a potential deficit in the host's ability to induce and/or maintain long-term protective antibodies. This is further supported by reports of frequent repeat infections with B. burgdorferi in endemic areas. The mechanisms underlying such a lack of long-term humoral immunity, however, remain unknown. We show here that B. burgdorferi infected mice show a similar rapid disappearance of Borrelia-specific antibodies after infection and subsequent antibiotic treatment. This failure was associated with development of only short-lived germinal centers, micro-anatomical locations from which long-lived immunity originates. These showed structural abnormalities and failed to induce memory B cells and long-lived plasma cells for months after the infection, rendering the mice susceptible to reinfection with the same strain of B. burgdorferi. The inability to induce long-lived immune responses was not due to the particular nature of the immunogenic antigens of B. burgdorferi, as antibodies to both T-dependent and T-independent Borrelia antigens lacked longevity and B cell memory induction. Furthermore, influenza immunization administered at the time of Borrelia infection also failed to induce robust antibody responses, dramatically reducing the protective antiviral capacity of the humoral response. Collectively, these studies show that B. burgdorferi-infection results in targeted and temporary immunosuppression of the host and bring new insight into the mechanisms underlying the failure to develop long-term immunity to this emerging disease threat. SN - 1553-7374 UR - https://www.unboundmedicine.com/medline/citation/26136236/Suppression_of_Long_Lived_Humoral_Immunity_Following_Borrelia_burgdorferi_Infection_ L2 - http://dx.plos.org/10.1371/journal.ppat.1004976 DB - PRIME DP - Unbound Medicine ER -