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

BUSSI, C; PERALTA RAMOS, JM; IRIBARREN, P; ARROYO, DS

Mar del Plata

Congreso; LXIV reunion anual. Sociedad Argentina de Inmunologia (SAI) SAIC; 2016

SAI - SAIC

Brain-resident microglia (Mi) and peripheral recruitedleukocytes, play essential roles in shaping the immuneresponse in the central nervous system (CNS). Thesecells activate and migrate in response to chemokinesproduced during active immune responses and may contributeto 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 tothe CNS and highlighted the importance of this processfor brain protection/repair. In this study, we assessedthe participation of type I-II IFNs in the innate immuneresponse displayed by tissue-resident microglia and recruited inflammatory leukocytes, to better understandthe contribution of these cytokines in the establishmentand development of a neuroinflammatory process inducedby systemic TLR4 stimulation. We characterized the molecularand cellular players involved in neuroinflammationinduced by i.p. administration of lipopolysaccharide (LPS- 1.6 mg/kg) to IFN-γ-/- and IFNAR-/- C57BL/6 mice, usingflow cytometry combined with confocal microscopy. Followingstimulation with LPS, we didn´t find any variationof CD11b+CD45lo microglial cells; however, we noticeda decrease of CD11b+CD45hi (Ly6Chi/CD11c+) myeloidrecruited leukocytes in both KO mice strains compared to their WT-treated counterparts (p<0.05). Unexpectedly, nosignificant changes were observed neither in the absolutenumber of MHC-II+ cells nor in the MFI of Mi and peripheralleukocytes. Interestingly, we found an increase ofCD11b+CD45hiLy6C+Ly6G+ neutrophils from LPS primedIFNAR-/- mice in comparison with their IFN-γ-/- littermates(p<0.05). Thereby, IFNs could prove to be important playersin the regulation of leukocyte recruitment to the CNSby controlling the innate immune response in neuroinflammation.Furthermore, these findings highlight the abilityof a systemic TLR4-mediated challenge to signal to theCNS and alter brain´s primary immunity.