RGD Reference Report - Streptococcus pneumoniae worsens cerebral ischemia via interleukin 1 and platelet glycoprotein Ibα. - Rat Genome Database

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Streptococcus pneumoniae worsens cerebral ischemia via interleukin 1 and platelet glycoprotein Ibα.

Authors: Dénes, Ádám  Pradillo, Jesus M  Drake, Caroline  Sharp, Andrew  Warn, Peter  Murray, Katie N  Rohit, Bazaz  Dockrell, David H  Chamberlain, Janet  Casbolt, Helen  Francis, Sheila  Martinecz, Bernadett  Nieswandt, Bernhard  Rothwell, Nancy J  Allan, Stuart M 
Citation: Dénes Á, etal., Ann Neurol. 2014 May;75(5):670-83. doi: 10.1002/ana.24146. Epub 2014 Apr 14.
RGD ID: 42722626
Pubmed: PMID:24644058   (View Abstract at PubMed)
DOI: DOI:10.1002/ana.24146   (Journal Full-text)


OBJECTIVE: Bacterial infection contributes to diverse noninfectious diseases and worsens outcome after stroke. Streptococcus pneumoniae, the most common infection in patients at risk of stroke, is a major cause of prolonged hospitalization and death of stroke patients, but how infection impacts clinical outcome is not known.
METHODS: We induced sustained pulmonary infection by a human S. pneumoniae isolate in naive and comorbid rodents to investigate the effect of infection on vascular and inflammatory responses prior to and after cerebral ischemia.
RESULTS: S. pneumoniae infection triggered atherogenesis, led to systemic induction of interleukin (IL) 1, and profoundly exacerbated (50-90%) ischemic brain injury in rats and mice, a response that was more severe in combination with old age and atherosclerosis. Systemic blockade of IL-1 with IL-1 receptor antagonist (IL-1Ra) fully reversed infection-induced exacerbation of brain injury and functional impairment caused by cerebral ischemia. We show that infection-induced systemic inflammation mediates its effects via increasing platelet activation and microvascular coagulation in the brain after cerebral ischemia, as confirmed by reduced brain injury in response to blockade of platelet glycoprotein (GP) Ibα. IL-1 and platelet-mediated signals converge on microglia, as both IL-1Ra and GPIbα blockade reversed the production of IL-1α by microglia in response to cerebral ischemia in infected animals.
INTERPRETATION: S. pneumoniae infection augments atherosclerosis and exacerbates ischemic brain injury via IL-1 and platelet-mediated systemic inflammation. These mechanisms may contribute to diverse cardio- and cerebrovascular pathologies in humans.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
brain ischemia exacerbatesISOGp1ba (Mus musculus)42722626; 42722626associated with Pneumococcal InfectionsRGD 
brain ischemia exacerbatesIMP 42722626associated with Pneumococcal InfectionsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gp1ba  (glycoprotein Ib platelet subunit alpha)

Genes (Mus musculus)
Gp1ba  (glycoprotein 1b, alpha polypeptide)

Genes (Homo sapiens)
GP1BA  (glycoprotein Ib platelet subunit alpha)


Additional Information