Expansion and preferential activation of the CD14⁺CD16⁺ monocyte subset during multiple sclerosis

Abstract

Multiple sclerosis (MS) is an immune-driven, demyelinating disease of the central nervous system (CNS). Although many types of immune cells are involved in disease progression, activated monocytes are believed to be one of the first to arrive to the brain and initiate inflammation. However, little is known about how the two main monocyte subsets, CD14(++)CD16(-) and CD14(+)CD16(+), are involved in MS. To understand how the phenotype and responses of these monocyte subsets are altered during MS, total monocytes and the purified monocyte subsets from healthy subjects (n=29) and MS patients (n=20) were characterized ex vivo and stimulated in vitro with lipopolysaccharide (LPS). The ex vivo analyses showed that total monocytes from MS patients had significantly elevated levels of CD40, CD86, HLA-DR, CD64 and C-C motif chemokine receptor 2 (CCR2), and this elevation was most marked on CD16(+) monocytes. In vitro stimulation with LPS led to an increase in CD86, HLA-DR, CD64 and IL-6 production by monocytes from MS patients. Furthermore, in purified cultures, CD14(+) monocytes were found to be the main producers of IL-10 while CD16(+) monocytes produced more IL-12. In monocytes from MS patients, both subsets produced substantially more IL-6, and the production of IL-10 by the CD16(+) subset was also significantly elevated compared with healthy monocytes. Together these findings highlight the important contribution of the CD16(+) monocyte subset in driving inflammatory responses during MS.

Evolving Identification of Blood Cells Associated with Clinically Isolated Syndrome: Importance of Time since Clinical Presentation and Diagnostic MRI

“…This finding is supported by recent publications analysing CD16+ monocytes and their gene expression in peripheral blood and the CSF of people with MS [16,17]. CD16+ monocytes from MS patients tend to have increased surface expression of activation markers and respond more robustly with inflammatory cytokine production to in vitro stimulation compared with cells from healthy controls [18,19]. Unless the similarity between HC and CIS is an effect of the small sample size of our early CIS group, these findings suggest that CIS is immunologically distinct from ODC (including MS) in their capacity for immune cells to stabilise to “normal” levels after a demyelinating event in the CNS.…”

Analysis of IL-6, IL-1β and TNF-α production in monocytes isolated from multiple sclerosis patients treated with disease modifying drugs

“…In this study, we show that the amount of IL-6 produced by classically stimulated monocytes was significantly greater from RRMS subjects compared to HC. This finding is in accordance with other reports [16, 17]. Unique to this study is that the significance of this difference is driven by RRMS subjects that are taking DMF, whose activated monocytes produced more IL-6 than RRMS patients taking other DMDs.…”

IL-12–producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion

“…+ monocytes has also been described in other conditions (37), e.g., multiple sclerosis (38) and Trypanosoma cruzi infection (39), but so far -to our knowledge -was not observed during HCMV infection or linked to the expansion of NKG2C + NK cells. Polymorphisms in innate cytokine signaling, e.g., in TLR2, in the IL-12 promoter, or in the IL-12 receptor, have been shown to affect immune responses in different infections including HCMV (40)(41)(42)(43).…”