Participation of INF gamma in IL-12 plus IL-18-induced neuroinflammation.

GAVIGLIO EMILIA A; PERALTA-RAMOS JAVIER M; ARROYO DANIELA S; BUSSI CLAUDIO; RODRIGUEZ GALÁN MARÍA C; IRIBARREN PABLO

Mar del Plata

Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología; 2014

Sociedad Argentina de Inmunología

Microglial cells (MC) are key immune cells within the central nervous system (CNS). They participate in CNS homeostasis and become activated once they contact pro-inflammatory signals. Some CNS injuries are accompanied by cell infiltration, which could contribute to tissue damage and to induce persistent activation of MC. Hydrodynamic injection of IL-12 and IL-18 cDNAs has previously been reported to generate high and persistent systemic levels of IL-12, IL-18 as well as IFN gamma (IFNg) and TNF alpha (TNFa) and to induce leukocyte recruitment and activation of MC in the brain. Since IL-12 and IL-18 were able to induce increased levels of IFNg and TNFa in mice, we wanted to evaluate the impact of systemic absence of TNFa or IFNg on the neuroinflammatory response. Therefore C57BL/6J, TNFa KO and IFNg KO mice were injected intravenously by hydrodynamic shear with the cDNAs for IL-12 plus IL-18 or control plasmid. Seven days after injection, mice were sacrificed perfused with HBSS and brains were collected. Cells suspensions were obtained for analysis of brain inflammatory cells using flow cytometry. Data demonstrated that the effects of hydrodynamic injection of IL-12 plus IL-18 were not affected by the absence of TNFa, however, IFNg deficiency decreased the number of recruited cells (CD45 high CD11b+) (p<0,05), which were mainly CD45 high CD11b+ Ly6C+ (p<0,05). Besides, IFNg KO mice hydrodynamically injected showed reduced levels of MHC II molecules in both parenchymal MC (CD11b+CD45 low) (p<0,01) and CD45 high CD11b+(p<0,001) recruited cells, compared with WT mice. Moreover, in IFNg KO mice the hydrodynamic injection of IL-12 and IL-18 failed to induce splenomegaly (p>0,05). Systemic expression of IL-12 and IL-18, in the absence of LPS, induces leukocyte recruitment to the brain and activation of resident MC. Interestingly, IFNg seems to participate in monocyte recruitment into the CNS and activation of resident MC.