Phosphatidyl-Inositol-3 kinase inhibitors regulate peptidoglycan-induced myeloid leukocyte recruitment, inflammation, and neurotoxicity in mouse brain

ARROYO, DANIELA S.; GAVIGLIO, EMILIA A.; RAMOS, JAVIER M. PERALTA; BUSSI, CLAUDIO; AVALOS, MARIA P.; CANCELA, LILIANA M.; IRIBARREN, PABLO

Frontiers in Immunology

Frontiers Media S.A.

Lugar: Lausana; Año: 2018 vol. 9

cute brain injury leads to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral myeloid cells (MC), which contribute to the inflammatory response involved in neuronal damage. We previously reported that TLR2 stimulation by peptidoglycan (PGN) from Staphylococcus aureus, in vitro and in vivo, induced microglial cell activation followed by autophagy induction. In this report, we evaluated if phosphatidyl-inositol-3 kinase (PI3K) pharmacological inhibitors LY294200 and 3-methyladenine (3-MA) can modulate the innate immune response to PGN in the central nervous system. We found that injection of PGN into the mouse brain parenchyma (caudate putamen) triggered an inflammatory reaction, which involved activation of microglial cells, recruitment of infiltrating MC to injection site, production of pro-inflammatory mediators, and neuronal injury. In addition, we observed the accumulation of LC3B+ CD45+ cells and colocalization of LC3B and lysos