Participation of type I-II IFNs in the regulation of the CNS immune surveillance after systemic inflammation.

PERALTA-RAMOS JAVIER M; BUSSI CLAUDIO; ARROYO DANIELA S; IRIBARREN PABLO

Congreso; LXIV Reunión Anual de la SAI; 2016

Brain-resident microglia (Mi) and peripheral recruited leukocytes, play essential roles in shaping the immune response in the central nervous system (CNS). These cells activate and migrate in response to chemokines produced during active immune responses and may contribute to the progression of neuroinflammation. Recent findings have revealed distinct roles for type I (α and β)-II (γ) interferons (IFNs) in the recruitment of immune cells to the CNS and highlighted the importance of this process for brain protection/repair. In this study, we assessed the participation of type I-II IFNs in the innate immune response displayed by tissue-resident microglia and recruited inflammatory leukocytes, to better understand the contribution of these cytokines in the establishment and development of a neuroinflammatory process induced by systemic TLR4 stimulation. We characterized the molecular and cellular players involved in neuroinflammation induced by i.p. administration of lipopolysaccharide (LPS - 1.6 mg/kg) to IFN-γ-/- and IFNAR-/- C57BL/6 mice, using flow cytometry combined with confocal microscopy. Following stimulation with LPS, we didn´t find any variation of CD11b+CD45lo microglial cells; however, we noticed a decrease of CD11b+CD45hi (Ly6Chi/CD11c+) myeloid recruited leukocytes in both KO mice strains compared to their WT-treated counterparts (p<0.05). Unexpectedly, no significant changes were observed neither in the absolute number of MHC-II+ cells nor in the MFI of Mi and peripheral leukocytes. Interestingly, we found an increase of CD11b+CD45hiLy6C+Ly6G+ neutrophils from LPS primed IFNAR-/- mice in comparison with their IFN-γ-/- littermates (p<0.05). Thereby, IFNs could prove to be important players in the regulation of leukocyte recruitment to the CNS by controlling the innate immune response in neuroinflammation. Furthermore, these findings highlights the ability of a systemic TLR4-mediated challenge to signal to the CNS and alter brain´s primary immunity.