Elevated interferon-gamma in CNS inflammatory disease: a potential complication for bone marrow reconstitution in MS

Hassan‐Zahraee, Mina; Bourbonnière, Lyne; Owens, Trevor

doi:10.1016/s0165-5728(99)00263-5

Cited by 5 publications

(3 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animals were evaluated for their responses to an intracerebral inoculation of S. aureus at approx. 10–12 weeks following bone marrow transfer, a period that we, and others (Hassan-Zahraee et al, 2000; Becher et al, 2001; Zehntner et al, 2004), have established to be sufficient for establishing chimaerism. We found that bone marrow chimaeras generated with B6/SJL and MyD88 KO mice did not exhibit any evidence of graft versus host disease, indicating that this was not a confounding issue.…”

Section: Methodsmentioning

confidence: 80%

MyD88 Expression by CNS-Resident Cells is Pivotal for Eliciting Protective Immunity in Brain Abscesses

et al. 2009

View full text Add to dashboard Cite

MyD88 KO (knockout) mice are exquisitely sensitive to CNS (central nervous system) infection with Staphylococcus aureus, a common aetiological agent of brain abscess, exhibiting global defects in innate immunity and exacerbated tissue damage. However, since brain abscesses are typified by the involvement of both activated CNS-resident and infiltrating immune cells, in our previous studies it has been impossible to determine the relative contribution of MyD88-dependent signalling in the CNS compared with the peripheral immune cell compartments. In the present study we addressed this by examining the course of S. aureus infection in MyD88 bone marrow chimaera mice. Interestingly, chimaeras where MyD88 was present in the CNS, but not bone marrow-derived cells, mounted pro-inflammatory mediator expression profiles and neutrophil recruitment equivalent to or exceeding that detected in WT (wild-type) mice. These results implicate CNS MyD88 as essential in eliciting the initial wave of inflammation during the acute response to parenchymal infection. Microarray analysis of infected MyD88 KO compared with WT mice revealed a preponderance of differentially regulated genes involved in apoptotic pathways, suggesting that the extensive tissue damage characteristic of brain abscesses from MyD88 KO mice could result from dysregulated apoptosis. Collectively, the findings of the present study highlight a novel mechanism for CNS-resident cells in initiating a protective innate immune response in the infected brain and, in the absence of MyD88 in this compartment, immunity is compromised.

show abstract

Section: Methodsmentioning

confidence: 80%

MyD88 Expression by CNS-Resident Cells is Pivotal for Eliciting Protective Immunity in Brain Abscesses

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Polymorphisms in the IFN-γ gene or in the downstream signaling pathway may be associated with brainstem inflammation and vertigo. IFN-γ may be characterized by differential chemokine expression patterns, increased encephalitogenic T cell proliferation, and the accumulation of polymorphonuclear infiltrate in the brain parenchyma [15,38]. In comparison to healthy individuals, patients with acute vestibular neuritis had significantly elevated plasma levels of the pro-inflammatory mediators TNF-α and COX-2 [23].…”

Section: Discussionmentioning

confidence: 99%

Exercise suppresses COX-2 pro-inflammatory pathway in vestibular migraine

Lee

Yi²,

Huang

et al. 2015

Brain Research Bulletin

View full text Add to dashboard Cite

“…27 After 7 weeks, mice were placed onto a 0.2% cuprizone diet and sacrificed after 3 or 4.5 weeks of treatment. Chimeric mice that were not treated with cuprizone were also sacrificed at equivalent time points.…”

Section: Bone Marrow Chimerasmentioning

confidence: 99%

Microglial Recruitment, Activation, and Proliferation in Response to Primary Demyelination

Remington

Babcock

Zehntner

et al. 2007

The American Journal of Pathology

Self Cite

208

206

View full text Add to dashboard Cite

We have characterized the cellular response to demyelination/remyelination in the central nervous system using the toxin cuprizone, which causes reproducible demyelination in the corpus callosum. Microglia were distinguished from macrophages by relative CD45 expression (CD45 dim ) using flow cytometry. Their expansion occurred rapidly and substantially outnumbered infiltrating macrophages and T cells throughout the course of cuprizone treatment. We used bromodeoxyuridine incorporation and bone marrow chimeras to show that both proliferation and immigration from blood accounted for increased microglial numbers. Microglia adopted an activated phenotype during demyelination, up-regulating major histocompatibility class I and B7.2/CD86. A subpopulation of CD45 dim-high microglia that expressed reduced levels of CD11b emerged during demyelination. These microglia expressed CD11c and were potent antigen-presenting cells in vitro. T cells were recruited to the demyelinated corpus callosum but did not appear to be activated. Our study highlights the role of microglia as a heterogeneous population of cells in primary demyelination, with the capacity to present antigen, proliferate, and migrate into demyelinated areas.

show abstract

Elevated interferon-gamma in CNS inflammatory disease: a potential complication for bone marrow reconstitution in MS

Cited by 5 publications

References 24 publications

MyD88 Expression by CNS-Resident Cells is Pivotal for Eliciting Protective Immunity in Brain Abscesses

MyD88 Expression by CNS-Resident Cells is Pivotal for Eliciting Protective Immunity in Brain Abscesses

Exercise suppresses COX-2 pro-inflammatory pathway in vestibular migraine

Microglial Recruitment, Activation, and Proliferation in Response to Primary Demyelination

Contact Info

Product

Resources

About