IgG Immune Complexes Break Immune Tolerance of Human Microglia

Marlijn van der Poel, Willianne Hoepel, J. rg Hamann, Inge Huitinga, Jeroen den Dunnen

Research output: Contribution to JournalArticleAcademicpeer-review

11 Citations (Scopus)

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 I:C, resulting in increased production of key proinflammatory cytokines, such as TNF and IL-1b. We identified FcgRI and FcgRIIa 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.

Original languageEnglish
Pages (from-to)2511-2518
Number of pages8
JournalJournal of immunology (Baltimore, Md.
Volume205
Issue number9
DOIs
Publication statusPublished - 1 Nov 2020

Cite this