Characterization of nucleotide-binding oligomerization domain (NOD) protein expression in primary murine microglia

Sterka, David; Marriott, Ian

doi:10.1016/j.jneuroim.2006.06.009

Cited by 55 publications

(83 citation statements)

References 51 publications

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“…Microglia are the main innate immune cells safeguarding the neuronal tissue. Like other innate immune cells, microglia express pattern-recognition receptors (PRRs), including toll-like receptors (TLRs) 1,2 and NOD-like receptors (NLRs), 3 which can bind various pathogen-associated molecular patterns (PAMPs), leading to microglial activation. In addition to PRRs, various other molecules are also involved in microglial activation.…”

Section: Discussionmentioning

confidence: 99%

Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation

Chen

Luo²,

Peñalva³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To investigate the role of the Fractalkine receptor CX3CR1 pathway in oxidative insults-mediated retinal degeneration and immune activation. RESULTS. Intravitreal injection of paraquat (0.75 lM) resulted in acute retinal capillary nonperfusion within 2 days, which improved from 4 days to 4 weeks postinjection (p.i.). Panretinal degeneration was observed at 4 days p.i. and progressed further at 4 weeks p.i. In the absence of CX3CR1, retinal degeneration was exaggerated and was accompanied by increased TNF-a, iNOS, IL-1b, Ccl2, and Casp-1 gene expression. Confocal microscopy of retinal flatmounts revealed microglial activation and CD44 þ MHC-II þ monocyte and GR1 þ neutrophil infiltration in paraquat-injected eyes. The number of activated microglia and infiltrating leukocytes was significantly higher in CX3CR1 gfp/gfp mice than in CX3CR1 gfp/þ mice. CONCLUSIONS.Our results suggest that the CX3CR1 signaling pathway may play an important role in controlling retinal inflammation under oxidative and ischemia/reperfusion conditions. In the absence of CX3CR1, uncontrolled retinal inflammation results in exaggerated retinal degeneration. (Invest Ophthalmol Vis Sci. 2013;54:682-690)

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Section: Discussionmentioning

confidence: 99%

Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation

Chen

Luo²,

Peñalva³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…Mouse neonatal brain astrocytes were isolated, as described previously by our laboratory (6,13,20,21), and cultured in RPMI 1640 containing 10% FBS. Cells isolated in this manner are Ͼ97% authentic astrocytes due to their characteristic morphology, expression of glial fibrillary acidic protein, and the absence of CD11b as determined by immunofluorescent microscopy.…”

Section: Isolation and Characterization Of Primary Murine Astrocytesmentioning

confidence: 99%

“…A clonal low passage of B. burgdorferi strain N40 was used throughout these studies and was grown in BSK II medium while N. meningitidis strain MC58 was grown overnight in 5 ml of GC medium plus hemoglobin with Isovitalex enrichment solution at 37°C, as previously described (6,20). For cell lysates, bacteria were centrifuged at 10,000 ϫ g and washed three times with PBS before pulsing three times with a cell sonicator.…”

Section: Culture Of B Burgdorferi and Neisseria Meningitidis And Prementioning

confidence: 99%

“…For cell lysates, bacteria were centrifuged at 10,000 ϫ g and washed three times with PBS before pulsing three times with a cell sonicator. B. burgdorferi Ag isolates generated in this manner have previously been demonstrated to be free of detectable levels of LPS (6,7,17,19). For in vitro exposure of isolated glia to N. meningitidis or B. burgdorferi, bacteria were harvested by centrifugation and washed twice in PBS.…”

Section: Culture Of B Burgdorferi and Neisseria Meningitidis And Prementioning

confidence: 99%

“…Although the brain has traditionally been viewed as a "victim organ" of infiltrating leukocytes, it has become increasingly apparent that resident glial cells, such as microglia and astrocytes, play an important role in the initiation and/or progression of immune responses following pathogen invasion. These glial cells can perceive bacteria via microbial pattern recognition receptors, including members of the TLR and nucleotide-binding domain leucine rich repeat region containing (NLR) receptor families, to promote recruitment and Ag-specific activation of infiltrating leukocytes (2)(3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

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Neurogenic Exacerbation of Microglial and Astrocyte Responses toNeisseria meningitidisandBorrelia burgdorferi

Chauhan

Sterka

Gray

et al. 2008

The Journal of Immunology

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109

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Although glial cells are recognized for their roles in maintaining neuronal function, there is growing appreciation of the ability of resident CNS cells to initiate and/or augment inflammation following trauma or infection. The tachykinin, substance P (SP), is well known to augment inflammatory responses at peripheral sites and its presence throughout the CNS raises the possibility that this neuropeptide might serve a similar function within the brain. In support of this hypothesis, we have recently demonstrated the expression of high affinity receptors for SP (Neurokinin-1 (NK-1) receptors) on microglia and shown that this tachykinin can significantly elevate bacterially induced inflammatory prostanoid production by isolated cultures of these cells. In the present study, we demonstrate that endogenous SP/NK-1R interactions are an essential component in the initiation and/or progression of CNS inflammation in vivo following exposure to two clinically relevant bacterial CNS pathogens, Neisseria meningitidis and Borrelia burgdorferi. We show that in vivo elevations in inflammatory cytokine production and decreases in the production of an immunosuppressive cytokine are markedly attenuated in mice genetically deficient in the expression of the NK-1R or in mice treated with a specific NK-1R antagonist. Furthermore, we have used isolated cultures of microglia and astrocytes to demonstrate that SP can augment inflammatory cytokine production by these resident CNS cell types following exposure to either of these bacterial pathogens. Taken together, these studies indicate a potentially important role for neurogenic exacerbation of resident glial immune responses in CNS inflammatory diseases, such as bacterial meningitis.

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NOD2 plays an important role in the inflammatory responses of microglia and astrocytes to bacterial CNS pathogens

Chauhan

Sterka

Furr

et al. 2008

Glia

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While glial cells are recognized for their roles in maintaining neuronal function, there is growing appreciation that resident central nervous system (CNS) cells initiate and/or augment inflammation following trauma or infection. We have recently demonstrated that microglia and astrocytes constitutively express nucleotide-binding oligomerization domain-2 (NOD2), a member of the novel nucleotide-binding domain leucine-rich repeat region containing family of proteins (NLR) that functions as an intracellular receptor for a minimal motif present in all bacterial peptidoglycans. In the present study, we have confirmed the functional nature of NOD2 expression in astrocytes and microglia and begun to determine the relative contribution that this NLR makes in inflammatory CNS responses to clinically relevant bacterial pathogens. We demonstrate the increased association of NOD2 with its downstream effector molecule, Rip2 kinase, in primary cultures of murine microglia and astrocytes following exposure to bacterial antigens. We show that this cytosolic receptor underlies the ability of muramyl dipeptide to augment the production of inflammatory cytokines by glia following exposure to specific ligands for disparate Toll-like receptor homologues. In addition, we demonstrate that NOD2 is an important component in the in vitro inflammatory responses of resident glia to N. meningitidis and B. burgdorferi antigens. Finally, we have established that NOD2 is required, at least in part, for the astrogliosis, demyelination, behavioral changes, and elevated inflammatory cytokine levels observed following in vivo infection with these pathogens. As such, we have identified NOD2 as an important component in the generation of damaging CNS inflammation following bacterial infection.

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Characterization of nucleotide-binding oligomerization domain (NOD) protein expression in primary murine microglia

Cited by 55 publications

References 51 publications

Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation

Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation

Neurogenic Exacerbation of Microglial and Astrocyte Responses toNeisseria meningitidisandBorrelia burgdorferi

NOD2 plays an important role in the inflammatory responses of microglia and astrocytes to bacterial CNS pathogens

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