Expression and distribution of Toll‐like receptors in the brain during murine neurocysticercosis

Mishra, Bibhuti B.; Mishra, Pramod Kumar; Teale, Judy M.

doi:10.1016/j.jneuroim.2006.07.019

Cited by 148 publications

(158 citation statements)

References 54 publications

(52 reference statements)

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“…Similar findings have also been made for lack of TLR2 protein expression by astrocytes in two murine lesion models (Babcock et al, 2006;Wainwright et al, 2010). The fact that TLR2 protein expression was detected on astrocytes in murine neurocysticercosis (Mishra et al, 2006) suggests that astrocyte TLR2 expression may depend on the strength of induction signal.…”

Section: Introductionsupporting

confidence: 78%

Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response

Holm

Dræby

Owens

2012

Glia

116

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Within the central nervous system, astrocytes and microglia are the primary responders to endogenous ligands released upon injury and stress, as well as to infectious pathogens. Toll-like receptors (TLRs) are implicated in recognition of both types of stimulus. Whether astrocytes respond as strongly as microglia to TLR agonists remains contentious. In this study, we have rigorously purified astrocytes to determine their capacity for autonomous TLR response, in absence of microglia. We used flow cytometry and differential adhesion as well as a myeloid lineage-specific suicide gene to purify astrocytes from mixed glial cultures and measured their response to TLR agonists. Our results show that the response of astrocytes to TLR2 and TLR3 agonists is greatly enhanced by, and response to TLR4 agonists is completely dependent on, the presence of functional microglia. In the case of the TLR4 response to lipopolysaccharide, microglia exert their effect on astrocytes at least partially through release of soluble mediators that directly activate or facilitate astrocyte responses. Our findings underline the contribution of glial crosstalk in CNS responses to injury or inflammation. V

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Section: Introductionsupporting

confidence: 78%

Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response

Holm

Dræby

Owens

2012

Glia

116

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“…The difference in this response was surprising because TLR9 is not readily detectable on choroid plexus cells by IHC analysis of mouse brain tissue. 25 However, analysis of gene expression of isolated choroid plexus demonstrated expression of Tlr9, Myd88, and Irf7 mRNA at comparable levels as those observed with astrocytes (Figure 8), indicating that these cells may be directly responding to CpG-ODN stimulation. A similar phenomenon is observed with lipopolysaccharide induction of TNF expression by ependymal cells, despite the lack of detectable TLR4 on these cells.…”

Section: Discussionmentioning

confidence: 78%

“…A similar phenomenon is observed with lipopolysaccharide induction of TNF expression by ependymal cells, despite the lack of detectable TLR4 on these cells. 25,28,29 The strong response of choroid plexus cells to CpG-ODN in this study may be due, in part, to the route of CpG-ODN. Analysis of agonists after ICV inoculation showed widespread distribution at 1 and 4 hpi, but staining was also intense in the ventricles themselves.…”

Section: Discussionmentioning

confidence: 83%

“…Expression of TLR9 on choroid epithelia or on ependymal cells has not been reported, and only low-level expression of TLR7 on ependymal cells has been observed. 25 We, therefore, examined choroid plexus from neonatal mice for their expression of Tlr7 and Tlr9 mRNA and compared this expression with that of purified astrocytes, which readily respond to TLR7 or TLR9 stimulation despite low levels of TLR7 or TLR9 expression, as well as microglia, which express higher levels of both receptors. Analysis of cell-specific mRNA expression of Ttr, Gfap, and F4/80 was used to verify the population of choroid plexus cells, astrocytes, and microglia (Figure 8, A-C).…”

Section: Source Of Cytokine Expression After In Vivo Inoculation Of Tmentioning

confidence: 99%

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TLR7 and TLR9 Trigger Distinct Neuroinflammatory Responses in the CNS

Butchi

Woods

et al. 2011

The American Journal of Pathology

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Toll-like receptors (TLRs) 7 and 9 recognize nucleic acid determinants from viruses and bacteria and elicit the production of type I interferons and proinflammatory cytokines. TLR7 and TLR9 are similar regarding localization and signal transduction mechanisms. However, stimulation of these receptors has differing effects in modulating viral pathogenesis and in direct toxicity in the central nervous system (CNS). In the present study, we examined the potential of the TLR7 agonist imiquimod and the TLR9 agonist cytosine-phosphateguanosine oligodeoxynucleotide (CpG-ODN) to induce neuroinflammation after intracerebroventricular inoculation. CpG-ODN induced a more robust inflammatory response than did imiquimod after inoculation into the CNS, with higher levels of several proinflammatory cytokines and chemokines. The increase in cytokines and chemokines correlated with breakdown of the bloodcerebrospinal fluid barrier and recruitment of peripheral cells to the CNS in CpG-ODN-inoculated mice. In contrast, TLR7 agonists induced a strong interferon ␤ response in the CNS but only low levels of other cytokines. The difference in response to these agonists was not due to differences in distribution or longevity of the agonists but rather was correlated with cytokine production by choroid plexus cells. These results indicate that despite the high similarity of TLR7 and TLR9 in binding nucleic acids and inducing similar downstream signaling, the neuroinflammation response induced by these receptors differs dramatically due, at least in part, to activation of cells in the choroid plexus.

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“…Murine primary cortical neurons express TLR2, 3 and 4 at the mRNA and protein level [12]. TLR2 and TLR6 protein was also shown to be expressed in primary brain neurons under control conditions, while protein levels for TLR4, 7 and 8 was induced by parasitic infection [13]. In contrast human neurons only express TLR3 [14], while Page 7 of 62 A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 7 both mouse and human microglia express mRNA for TLR1-9 [15] [16] (Table 1).…”

Section: Tlr Expression In Cells Of the Brainmentioning

confidence: 97%

Evaluating the role of Toll-like receptors in diseases of the central nervous system

Carty

Bowie

2011

Biochemical Pharmacology

134

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A key part of the innate immune system is a network of pattern recognition receptors (PRRs) and their associated intracellular signalling pathways. Toll-like receptors (TLRs) are one such group of PRRs that detect pathogen associated molecular patterns (PAMPs). Activation of the TLRs with their respective agonists results in the activation of intracellular signalling pathways leading to the expression of proinflammatory mediators and anti-microbial effector molecules. Activation of the innate immune system through TLRs also triggers the adaptive immune response, resulting in a comprehensive immune program to eradicate invading pathogens. It is now known that immune surveillance and inflammatory responses occur in the central nervous system (CNS). Furthermore it is becoming increasingly clear that TLRs have a role in such CNS responses andare also implicated in the pathogenesis of a number of conditions in the CNS, such as Alzheimer's, stroke and multiple sclerosis. This is likely due to the generation of endogenous TLR agonists in these conditions which amplifies a detrimental neurotoxic inflammatory response. However TLRs in some situations can be neuroprotective, if triggered in a favourable context. This review aims to examine the recent literature on TLRs in the CNS thus demonstrating their importance in a range of infectious and non-infectious diseases of the brain.

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Expression and distribution of Toll‐like receptors in the brain during murine neurocysticercosis

Cited by 148 publications

References 54 publications

Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response

Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response

TLR7 and TLR9 Trigger Distinct Neuroinflammatory Responses in the CNS

Evaluating the role of Toll-like receptors in diseases of the central nervous system

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