Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection

Rebecca A. Elsner, Christine J. Hastey, Kimberly J. Olsen, Nicole Baumgarth

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1004976
JournalPLoS Pathogens
Volume11
Issue number7
DOIs
StatePublished - Jul 1 2015

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Borrelia Infections
Borrelia burgdorferi
Humoral Immunity
Infection
Borrelia
Antibodies
Antibody Formation
Immunity
B-Lymphocytes
T Independent Antigens
Emerging Communicable Diseases
Anti-Bacterial Agents
Disease Vectors
Germinal Center
Lyme Disease
Plasma Cells
Immunosuppression
Human Influenza
Antiviral Agents
Immunization

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection. / Elsner, Rebecca A.; Hastey, Christine J.; Olsen, Kimberly J.; Baumgarth, Nicole.

In: PLoS Pathogens, Vol. 11, No. 7, e1004976, 01.07.2015.

Research output: Contribution to journalArticle

Elsner, Rebecca A. ; Hastey, Christine J. ; Olsen, Kimberly J. ; Baumgarth, Nicole. / Suppression of Long-Lived Humoral Immunity Following Borrelia burgdorferi Infection. In: PLoS Pathogens. 2015 ; Vol. 11, No. 7.
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