Bacterial peptidoglycan and immune reactivity in the central nervous system in multiple sclerosis

Abstract

SummaryMultiple sclerosis is believed to result from a CD4ϩ T-cell response against myelin antigens. Peptidoglycan, a major component of the Gram-positive bacterial cell wall, is a functional lipopolysaccharide analogue with potent proinflammatory properties and is conceivably a mediator of sterile inflammation. Here we demonstrate that peptidoglycan is present within antigen-presenting cells in the brain of multiple sclerosis patients. These cells have macrophage and dendritic cell characteristics,

Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response

“…Our data do not exclude the possibility of induction of such responsiveness by astrocytes in the highly inflammatory milieu of MS, where soluble mediator responses such as the one we have described may be more effective. The action of peptidoglycans and related molecules that have been demonstrated in the CNS in MS (Schrijver et al, 2001) may contribute to such a microglial-dependent astrogliosis.…”

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

“…100 Bacterial involvement in the pathogenesis of multiple sclerosis was suggested after the bacterial peptidoglycan was found within antigen presenting cells (dendritic cells and macrophages) in the brains of patients but not of control individuals. 101 The potential role of molecular mimicry associated with infections was studied by Westall. 58 By comparing the sequences from three known encephalitogenic peptides with all known human bacterial and viral agents, this group found that mimics are present in a wide variety of microorganisms. Interestingly, the mimics were present predominantly in non-pathogenic gut bacteria.…”

RIP kinases: key decision makers in cell death and innate immunity

“…Levels of RIP2 are elevated in the non-Tcell fraction of blood from multiple sclerosis (MS) subjects, 187 and pathogenesis in murine models of MS have been shown to be dependent on NOD1, NOD2 and RIP2 with the latter having an especially important role in activating CNS dendritic cells. 188 Intriguingly, peptidoglycan has been detected within antigen-presenting cells, including dendritic cells, in the brain of MS patients 189 suggesting that the peptidoglycan-NOD-RIP2 axis in CNS may contribute to MS pathogenesis. RIP2 has also been implicated as a driver in experimental allergic airway inflammation by activating NFkB and inflammatory gene expression.…”