CONICET | Buscador de Institutos y Recursos Humanos

Microglial cells (MC) are key immune cells within the centralnervous system (CNS). They participate in CNS homeostasis andbecome activated once they contact pro-inflammatory signals.Some CNS injuries are accompanied by cell infiltration, whichcould contribute to tissue damage and to induce persistent activationof MC. Hydrodynamic injection of IL-12 and IL-18 cDNAs haspreviously been reported to generate high and persistent systemiclevels of IL-12, IL-18 as well as IFN gamma (IFNg) and TNF alpha(TNFa) and to induce leukocyte recruitment and activation of MCin the brain. Since IL-12 and IL-18 were able to induce increasedlevels of IFNg and TNFa in mice, we wanted to evaluate the impactof systemic absence of TNFa or IFNg on the neuroinflammatoryresponse. Therefore C57BL/6J, TNFa KO and IFNg KO mice wereinjected intravenously by hydrodynamic shear with the cDNAs forIL-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 inflammatorycells using flow cytometry. Data demonstrated that the effects ofhydrodynamic injection of IL-12 plus IL-18 were not affected bythe absence of TNFa, however, IFNg deficiency decreased thenumber of recruited cells (CD45 high CD11b+) (p<0.05), whichwere mainly CD45 high CD11b+ Ly6C+ (p<0.05). Besides, IFNgKO mice hydrodynamically injected showed reduced levels of MHCII molecules in both parenchymal MC (CD11b+CD45 low) (p<0.01)and CD45 high CD11b+(p<0,001) recruited cells, compared withWT mice. Moreover, in IFNg KO mice the hydrodynamic injection ofIL-12 and IL-18 failed to induce splenomegaly (p>0.05). Systemicexpression of IL-12 and IL-18, in the absence of LPS, inducesleukocyte recruitment to the brain and activation of resident MC.Interestingly, IFNg seems to participate in monocyte recruitmentinto the CNS and activation of resident MC.