IgG Immune Complexes Break Immune Tolerance of Human Microglia.
J Immunol
; 205(9): 2511-2518, 2020 11 01.
Article
em En
| MEDLINE
| ID: mdl-32967931
ABSTRACT
Microglia are phagocytic cells involved in homeostasis of the brain and are key players in the pathogenesis of multiple sclerosis (MS). A hallmark of MS diagnosis is the presence of IgG Abs, which appear as oligoclonal bands in the cerebrospinal fluid. In this study, we demonstrate that myelin obtained post mortem from 8 out of 11 MS brain donors is bound by IgG Abs. Importantly, we show that IgG immune complexes strongly potentiate activation of primary human microglia by breaking their tolerance for microbial stimuli, such as LPS and Poly IC, resulting in increased production of key proinflammatory cytokines, such as TNF and IL-1ß. We identified FcγRI and FcγRIIa as the two main responsible IgG receptors for the breaking of immune tolerance of microglia. Combined, these data indicate that IgG immune complexes potentiate inflammation by human microglia, which may play an important role in MS-associated inflammation and the formation of demyelinating lesions.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina G
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Microglia
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Tolerância Imunológica
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Complexo Antígeno-Anticorpo
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Holanda