RGD Reference Report - Phosphatidylinositol 3-Kinase γ is required for the development of experimental cerebral malaria. - Rat Genome Database

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Phosphatidylinositol 3-Kinase γ is required for the development of experimental cerebral malaria.

Authors: Lacerda-Queiroz, Norinne  Brant, Fatima  Rodrigues, David Henrique  Vago, Juliana Priscila  Rachid, Milene Alvarenga  Sousa, Lirlândia Pires  Teixeira, Mauro Martins  Teixeira, Antonio Lucio 
Citation: Lacerda-Queiroz N, etal., PLoS One. 2015 Mar 16;10(3):e0119633. doi: 10.1371/journal.pone.0119633. eCollection 2015.
RGD ID: 38599200
Pubmed: PMID:25775137   (View Abstract at PubMed)
PMCID: PMC4361544   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0119633   (Journal Full-text)

Experimental cerebral malaria (ECM) is characterized by a strong immune response, with leukocyte recruitment, blood-brain barrier breakdown and hemorrhage in the central nervous system. Phosphatidylinositol 3-kinase γ (PI3Kγ) is central in signaling diverse cellular functions. Using PI3Kγ-deficient mice (PI3Kγ-/-) and a specific PI3Kγ inhibitor, we investigated the relevance of PI3Kγ for the outcome and the neuroinflammatory process triggered by Plasmodium berghei ANKA (PbA) infection. Infected PI3Kγ-/- mice had greater survival despite similar parasitemia levels in comparison with infected wild type mice. Histopathological analysis demonstrated reduced hemorrhage, leukocyte accumulation and vascular obstruction in the brain of infected PI3Kγ-/- mice. PI3Kγ deficiency also presented lower microglial activation (Iba-1+ reactive microglia) and T cell cytotoxicity (Granzyme B expression) in the brain. Additionally, on day 6 post-infection, CD3+CD8+ T cells were significantly reduced in the brain of infected PI3Kγ-/- mice when compared to infected wild type mice. Furthermore, expression of CD44 in CD8+ T cell population in the brain tissue and levels of phospho-IkB-α in the whole brain were also markedly lower in infected PI3Kγ-/- mice when compared with infected wild type mice. Finally, AS605240, a specific PI3Kγ inhibitor, significantly delayed lethality in infected wild type mice. In brief, our results indicate a pivotal role for PI3Kγ in the pathogenesis of ECM.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cerebral malaria  ISOPik3cg (Mus musculus)38599200; 38599200 RGD 
cerebral malaria  IMP 38599200 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pik3cg  (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma)

Genes (Mus musculus)
Pik3cg  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma)

Genes (Homo sapiens)
PIK3CG  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma)


Additional Information