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Published on: August 31, 2013
T Cells Exacerbate Lyme Borreliosis in TLR2-Deficient Mice
Carrie E Lasky1, Carmela L Pratt1, Kinsey A Hilliard1
1Department of Veterinary Pathobiology, University of Missouri , Columbia, MO , USA.
Abstract:
Infection of humans with the spirochete, Borrelia burgdorferi, causes Lyme borreliosis and can lead to clinical manifestations such as arthritis, carditis, and neurological conditions. Experimental infection of mice recapitulates many of these symptoms and serves as a model system for the investigation of disease pathogenesis and immunity. Innate immunity is known to drive the development of Lyme arthritis and carditis, but the mechanisms driving this response remain unclear. Innate immune cells recognize B. burgdorferi surface lipoproteins primarily via toll-like receptor (TLR)2; however, previous work has demonstrated TLR2-/- mice had exacerbated disease and increased bacterial burden. We demonstrate increased CD4 and CD8 T cell infiltrates in B. burgdorferi-infected joints and hearts of C3H TLR2-/- mice. In vivo depletion of either CD4 or CD8 T cells reduced Borrelia-induced joint swelling and lowered tissue spirochete burden, whereas depletion of CD8 T cells alone reduced disease severity scores. Exacerbation of Lyme arthritis correlated with increased production of CXCL9 by synoviocytes, and this was reduced with CD8 T cell depletion. These results demonstrate T cells can exacerbate Lyme disease pathogenesis and prolong disease resolution possibly through dysregulation of inflammatory responses and inhibition of bacterial clearance.
Insights
T cells, particularly CD8 T cells, can worsen Lyme disease symptoms and hinder bacterial clearance. Depleting these T cells in mice reduced joint swelling and bacterial load, suggesting a role in disease pathogenesis.
Area of Science:
- Immunology
- Microbiology
- Pathogenesis
Background:
- Lyme borreliosis, caused by *Borrelia burgdorferi*, presents with arthritis, carditis, and neurological issues.
- Innate immunity drives Lyme arthritis and carditis, but mechanisms are unclear.
- Toll-like receptor 2 (TLR2) recognizes *B. burgdorferi* lipoproteins, yet TLR2-deficient mice show worsened disease.
Purpose of the Study:
- Investigate the role of T cells in *Borrelia burgdorferi* infection and Lyme disease pathogenesis.
- Determine how T cell responses influence disease severity and bacterial burden.
- Elucidate mechanisms by which T cells may exacerbate Lyme arthritis.
Main Methods:
- Experimental infection of C3H mice with *Borrelia burgdorferi*.
- Analysis of T cell infiltrates (CD4 and CD8) in infected joints and hearts.
- In vivo depletion of CD4 and CD8 T cells to assess impact on disease.
Main Results:
- TLR2-deficient mice exhibited increased CD4 and CD8 T cell infiltrates in infected tissues.
- Depletion of CD4 or CD8 T cells reduced joint swelling and bacterial burden.
- Depletion of CD8 T cells alone decreased Lyme arthritis severity scores.
- Exacerbated arthritis correlated with increased CXCL9 production, reduced by CD8 T cell depletion.
Conclusions:
- T cells, specifically CD8 T cells, can exacerbate Lyme disease pathogenesis.
- T cell involvement may prolong disease resolution through inflammatory dysregulation.
- These findings highlight T cell-mediated exacerbation and impaired bacterial clearance in Lyme disease.
