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

PloS One
Norinne Lacerda-QueirozAntônio Lúcio Teixeira

Abstract

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-/- ...Continue Reading

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Citations

Jun 14, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Markus AckerknechtJens V Stein
Jun 21, 2018·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Sabrina TorrePhilippe Gros

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Methods Mentioned

BETA
electrophoresis
FCS
FACS
flow cytometry
ELISA

Software Mentioned

ImageJ
TreeStar
TreeAge
Image Pro - Plus
GraphPad Prism
GraphPad
FlowJo

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