Journal
FRONTIERS IN IMMUNOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2017.01666
Keywords
microglia; inflammatory monocytes; inflammation; lipopolysaccharide; interferons
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Funding
- Secretaria de Ciencia y Tecnologia from Universidad Nacional de Cordoba (SECyT)
- Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT)
- Fondo para la Investigacion Cientifica y Tecnologica (FONCyT)
- Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)
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Brain-resident microglia and peripheral migratory leukocytes play essential roles in shaping the immune response in the central nervous system. These cells activate and migrate in response to chemokines produced during active immune responses and may contribute to the progression of neuroinflammation. Herein, we addressed the participation of type I-II interferons in the response displayed by microglia and inflammatory monocytes to comprehend the contribution of these cytokines in the establishment and development of a neuroinflammatory process. Following systemic lipopolysaccharide (LPS) challenge, we found glial reactivity and an active recruitment of CD45(hi) leukocytes close to CD31(+) vascular endothelial cells in circumventricular organs. Isolated CD11b(+) CD45(hi) Ly6C(hi) Ly6G(-)-primed inflammatory monocytes were able to induce T cell proliferation, unlike CD11b(+) CD45(lo) microglia. Moreover, ex vivo re-stimulation with LPS exhibited an enhancement of T cell proliferative response promoted by inflammatory monocytes. These myeloid cells also proved to be recruited in a type I interferon-dependent fashion as opposed to neutrophils, unveiling a role of these cytokines in their trafficking. Together, our results compares the phenotypic and functional features between tissue-resident vs peripheral recruited cells in an inflamed microenvironment, identifying inflammatory monocytes as key sentinels in a LPS-induced murine model of neuroinflammation.
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