PARTICIPATION OF INTERFERON GAMMA IN THE LEUKOCYTE RECRUITMENT TO THE CENTRAL NERVOUS SYSTEM IN LPS-INDUCED NEUROINFLAMMATION

MANZONE-RODRÍGUEZ, C; PERALTA RAMOS, JM; BAEZ, NS; RODRÍGUEZ, CECILIA M.; ARROYO, DS; IRIBARREN, P

Buenos Aires

Congreso; Reunión de Sociedades de Biociencias (SAI, SAIC, AAFE, NANOMED-AR); 2021

Introduction: microglial cells are brain immune components incharge of maintaining the homeostasis and protecting the brain parenchymaagainst injuries.Peripheral leucocytes are recruited to the central nervous system(CNS) in response to cytokines and chemokines during neuroinflammatoryprocesses. If the response is not properly controlled, thatrecruitment could be harmful and may contribute to the progressionof neuroinflammation.We previously found that systemic lipopolysaccharide (LPS) challengeinduced glial activation and recruitment of CD45hi leukocytesto brain blood vessels, in circumventricular organs. During systemicinflammation interferon-gamma (IFN-γ) is induced and participatein the inflammation observed in different target organs. However,little is known about the impact of this cytokine in the CNSimmune cells during this process.Methods: we injected PBS or LPS (1.6 mg/kg, i.p.) to wild type (WT)C57BL/6 strain and IFN-γ knockout (KO) mice (n=4). After perfusion,we processed the brains to isolate the immune cells for stainingand measuring them by flow cytometry.We performed conventional and high dimensional flow cytometryanalysis to study the different immune cells populations.Results: LPS systemic stimuli increased the monocyte recruitmentto WT mice brains compared to PBS-injected control group (p<0.05).However, this effect was not observed in the IFN-γ KO mice (p NS),indicating that the presence of type II interferon participates in theresponse that results in the arrival of monocytes to the brain.Our preliminary results also showed increased lymphocytes recruit ment to the brains of LPS-stimulated WT mice, compared to controls(p<0.05). Nevertheless, that increase was impaired in the absenceof IFN-γ (p NS).Conclusion: during mice systemic inflammation, leukocyte recruitmentto CNS take place in a type II interferon-dependent manner,suggesting that this cytokine might be an important mediator of neuroinflammatoryresponses.Keywords: neuroinflammation, microglia, monocytes, type II interferon,LPS