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

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...

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Bibliographic Details
Published in:Infection and immunity 2014-04, Vol.82 (4), p.1548-1558
Main Authors: Hastey, Christine J, Ochoa, Jennine, Olsen, Kimberley J, Barthold, Stephen W, Baumgarth, Nicole
Format: Article
Language:English
Subjects:
Adaptor Proteins, Vesicular Transport - physiology
Analysis of Variance
Animals
B-Lymphocytes - cytology
Borrelia burgdorferi
Borrelia burgdorferi - immunology
Borrelia burgdorferi - pathogenicity
Chemokines - metabolism
Cytokines - metabolism
Cytokines - physiology
Disease Models, Animal
Gene Expression Profiling
Host Response and Inflammation
Immunity, Cellular
Interferon Type I - physiology
Lyme Disease - immunology
Lyme Disease - pathology
Lymph Nodes - immunology
Lymph Nodes - microbiology
Lymph Nodes - pathology
Mice
Mice, Inbred C57BL
Myeloid Differentiation Factor 88 - physiology
Receptors, Interferon - physiology
Signal Transduction - immunology
Time Factors
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Summary: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.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.00969-13