Toll-Like Receptors: Insights into Their Possible Role in the Pathogenesis of Lyme Neuroborreliosis

Bernardino, Andrea L. F.; Myers, Tereance A.; Álvarez, Xavier; Hasegawa, Atsuhiko; Philipp, Mario T.

doi:10.1128/iai.00394-08

Cited by 74 publications

(70 citation statements)

References 57 publications

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“…TLR2 also functions in host defense, as TLR2 Ϫ/Ϫ mice harbor higher spirochete burdens in target tissues than wild-type controls (27,28). Recent reports have also established a role for TLR5, a receptor for bacterial flagellin, as a mediator of B. burgdorferi-induced inflammation in murine cells (12,25). However, deficiency of either TLR2 or TLR5 significantly reduces, but does not completely abrogate, production of inflammatory cytokines by murine macrophages (12).…”

mentioning

confidence: 99%

Recognition of Borrelia burgdorferi, the Lyme Disease Spirochete, by TLR7 and TLR9 Induces a Type I IFN Response by Human Immune Cells

Petzke

Brooks

Krupna

et al. 2009

The Journal of Immunology

110

131

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Borrelia burgdorferi is the spirochetal agent of Lyme disease, a multisystemic disorder characterized by inflammation. Using global transcriptional profiling, we characterized the response of human PBMCs exposed to B. burgdorferi in an ex vivo coculture system. The expression profiles induced by B. burgdorferi were marked by the intense up-regulation of IFN-responsive transcripts and transcripts involved in the JAK/STAT signaling pathway. Transcript levels of IFN-α, IFN-β, and IRF7, and protein concentrations of IFN-α, were significantly elevated relative to those in unstimulated PBMCs. The induction of IFN-α was completely dependent upon phagocytosis of B. burgdorferi. Addition of a soluble type I IFN receptor, B18R, did not abolish the induction of IFN-inducible genes, indicating that B. burgdorferi directly elicits enhanced expression of these genes independently of type I IFN feedback signaling. Inhibitors of either TLR7 or TLR9 significantly reduced B. burgdorferi-stimulated IFN-α protein expression and transcription of IFN-induced genes. Simultaneous inhibition of both TLR7 and TLR9 completely abrogated IFN-α induction. The IFN-α-producing populations in PBMCs were identified as plasmacytoid dendritic and CD14+CD11c+ cells. These results reveal a TLR7/9-dependent signaling pathway used by human PBMCs to initiate a type I IFN response to the extracellular bacterium B. burgdorferi.

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confidence: 99%

Recognition of Borrelia burgdorferi, the Lyme Disease Spirochete, by TLR7 and TLR9 Induces a Type I IFN Response by Human Immune Cells

Petzke

Brooks

Krupna

et al. 2009

The Journal of Immunology

110

131

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“…Although most of the TLR research on Leptospira has focused on TLR2 and 4 (see below), studies on other spirochetes, particularly Borrelia burgdorferi, have shown that TLR5 (Bernardino et al 2008;Cabral et al 2006), TLR8 (Cervantes et al 2011), and TLR7 and TLR9 (Petzke et al 2009) also play a role in recognizing spirochetes. TLR1, TLR2 and TLR6 are structurally similar and can form heterodimers that are involved in lipoprotein detection, TLR5 detects the presence of flagellin, TLR7 and TLR8 recognize single stranded RNA and imidazoquinoline compounds, and TLR9 recognizes unmethylated CpG motifs in DNA .…”

Section: Toll-like Receptorsmentioning

confidence: 97%

Host Response to Leptospira Infection

Zuerner

2014

Current Topics in Microbiology and Immunology

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Pathogenic Leptospira has the capacity to infect a broad range of mammalian hosts. Leptospirosis may appear as an acute, potentially fatal infection in accidental hosts, or progress into a chronic, largely asymptomatic infection in natural maintenance hosts. The course that Leptospira infection follows is dependent upon poorly understood factors, but is heavily influenced by both the host species and bacterial serovar involved in infection. Recognition of pathogen-associated molecular patterns (PAMPs) by a variety of host pattern recognition receptors (PRRs) activates the host immune system. The outcome of this response may result in bacterial clearance, limited bacterial colonization of a few target organs, principally the kidney, or induction of sepsis as the host succumbs to infection and dies. This chapter describes current knowledge of how the host recognizes Leptospira and responds to infection using innate and acquired immune responses. Aspects of immune-mediated pathology and pathogen strategies to evade the host immune response are also addressed.

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“…OJEMD NF-κB is a transcription factor that regulates the expression of a large number of genes that are critical for the regulation of cellular process, such as inflammatory responses, apoptosis, and cell proliferation [12]. NF-κB pathways may promote central nervous system (CNS) cell survival through the inhibition of caspase-1 and -3 activity [13], and NF-κB as key mediators of the neuroprotective against inflammatory stress in nigral dopaminergic (DA) neurons [14].…”

Section: Discussionmentioning

confidence: 99%

Estrogen Receptor Alpha 36 Gene Knockdown Promote the Expression of NF-κB in PC12 Cells

Zou¹,

Qu²,

Xu³

et al. 2013

OJEMD

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The nuclear transcription factors κB (NF-κB) is widely existed in various kinds of cell types in the nervous system and plays an important role in neuron apoptosis and neurodegenerative diseases. Estrogen receptor alpha 36 (ER-α36) is a novel variant of ERα (as known ER-α66) which can transduce both estrogen-and antiestrogen-dependent activation of MAPK signal pathway and stimulate cell growth. Here, we aimed to detect the effect of ER-α36 gene silencing on the expression of NF-κB in normal cultured PC12 cells and to provide an experimental foundation for understanding the function of ER-α36 in nerve cells. PC12 cells with ER-α36 expression knocked down by the shRNA method. Then Western blot and immunocytochemical staining were performed to detect the expression and translocation of NF-κB after transfection. The results showed that NF-κB expression was significantly higher comparing with the control group after transfection (P < 0.01). Also, NF-κB subunit entered nuclear after transfection; Immunofluorescence staining and immunocytochemical staining of PC12 cells demonstrated that ER-α36 was expressed mainly on the plasma membrane and on the cell nucleus membrane. These data indicate that ER-α36 gene silencing can increase the expression of NF-κB and promote its nuclear translocation in PC12 cells.

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Toll-Like Receptors: Insights into Their Possible Role in the Pathogenesis of Lyme Neuroborreliosis

Cited by 74 publications

References 57 publications

Recognition of Borrelia burgdorferi, the Lyme Disease Spirochete, by TLR7 and TLR9 Induces a Type I IFN Response by Human Immune Cells

Recognition of Borrelia burgdorferi, the Lyme Disease Spirochete, by TLR7 and TLR9 Induces a Type I IFN Response by Human Immune Cells

Host Response to Leptospira Infection

Estrogen Receptor Alpha 36 Gene Knockdown Promote the Expression of NF-κB in PC12 Cells

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