Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice
Abstract
The Lyme disease vaccine is based on the outer-surface lipoprotein (OspA) of the pathogen Borrelia burgdorferi, and 95% of vaccine recipients develop substantial titers of antibodies against OspA. Here, we identified seven individuals with very low antibody titers after vaccination (low responders). The macrophages of low responders produced less tumor necrosis factor-alpha and interleukin-6 after OspA stimulation and had lower cell-surface expression of Toll-like receptor (TLR) 1 as compared to normal cells, but normal expression of TLR2. TLRs activate innate responses to pathogens, and TLR2 recognizes lipoproteins and peptidoglycan (PGN). After OspA immunization, mice genetically deficient in either TLR2 (TLR2(-/-)) or TLR1 (TLR1(-/-)) produced low titers of antibodies against OspA. Notably, macrophages from TLR2(-/-) mice were unresponsive to OspA and PGN, whereas those from TLR1(-/-) mice responded normally to PGN but not to OspA. These data indicate that TLR1 and TLR2 are required for lipoprotein recognition and that defects in the TLR1/2 signaling pathway may account for human hyporesponsiveness to OspA vaccination.
Cited By (16)
- Borrelia burgdorferiLipoprotein–Mediated TLR2 Stimulation Causes the Down‐Regulation of TLR5 in Human MonocytesThe Journal of Infectious Diseases · 2006
- Borrelia burgdorferiInduces TLR1 and TLR2 in Human Microglia and Peripheral Blood Monocytes but Differentially Regulates HLA-Class II ExpressionJournal of Neuropathology & Experimental Neurology · 2006
- Propensity to excessive proinflammatory response in chronic Lyme BorreliosisApmis · 2007
- Simultaneous Blocking of Human Toll-Like Receptors 2 and 4 Suppresses Myeloid Dendritic Cell Activation Induced byMycobacterium bovisBacillus Calmette-Guérin PeptidoglycanInfection and Immunity · 2003
- TLR activation triggers the rapid differentiation of Monocytes into macrophages and dendritic cellsNature Medicine · 2005
- Elucidation of Lyme arthritisNature reviews. Immunology · 2004
- Activation of innate host defense mechanisms by Borrelia
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