MyD88- and TRIF-independent induction of Type I interferon drives naive B cell accumulation but not loss of lymph node architecture in lyme disease

Christine J. Hastey, Jennine Ochoa, Kimberley J. Olsen, Stephen W Barthold, Nicole Baumgarth

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Rapidly after infection, live Borrelia burgdorferi, the causative agent of Lyme disease, is found within lymph nodes, causing rapid and strong tissue enlargement, a loss of demarcation between B cell follicles and T cell zones, and an unusually large accumulation of B cells. We sought to explore the mechanisms underlying these changes, as lymph tissue disruption could be detrimental for the development of robust Borrelia-specific immunity. A time course study demonstrated that the loss of the normal lymph node structure was a distinct process that preceded the strong increases in B cells at the site. The selective increases in B cell frequencies were due not to proliferation but rather to cytokine-mediated repositioning of B cells to the lymph nodes, as shown with various gene-targeted and bone marrow irradiation chimeras. These studies demonstrated that B. burgdorferi infection induced type I interferon receptor (IFNR) signaling in lymph nodes in a MyD88- and TRIF-independent manner and that type I IFNR indirect signaling was required for the excessive increases of naive B cells at those sites. It did not, however, drive the observed histopathological changes, which occurred independently also from major shifts in the lymphocyte-homing chemokines, CXCL12, CXCL13, and CCL19/21, as shown by quantitative reverse transcription-PCR (qRT-PCR), flow cytometry, and transwell migration experiments. Thus, B. burgdorferi infection drives the production of type I IFN in lymph nodes and in so doing strongly alters the cellular composition of the lymph nodes, with potential detrimental effects for the development of robust Borrelia-specific immunity.

Original languageEnglish (US)
Pages (from-to)1548-1558
Number of pages11
JournalInfection and Immunity
Volume82
Issue number4
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

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