Peptidoglycan-induced modulation of metabolic and inflammatory responses

Abstract

Bacterial cell wall peptidoglycan is composed of innate immune ligands and, due to its important structural role, also regulates access to many other innate immune ligands contained within the bacteria. There is a growing body of literature demonstrating how innate immune recognition impacts the metabolic functions of immune cells and how metabolic changes are not only important to inflammatory responses but are often essential. Peptidoglycan is primarily sensed in the context of the whole bacteria during lysosomal degradation; consequently, the innate immune receptors for peptidoglycan are primarily intracellular cytosolic innate immune sensors. However, during bacterial growth, peptidoglycan fragments are shed and can be found in the bloodstream of humans and mice, not only during infection but also derived from the abundant bacterial component of the gut microbiota. These peptidoglycan fragments influence cells throughout the body and are important for regulating inflammation and whole-body metabolic function. Therefore, it is important to understand how peptidoglycan-induced signals in innate immune cells and cells throughout the body interact to regulate how the body responds to both pathogenic and nonpathogenic bacteria. This mini-review will highlight key research regarding how cellular metabolism shifts in response to peptidoglycan and how systemic peptidoglycan sensing impacts whole-body metabolic function.

Role of Rab5 early endosomes in regulating Drosophila gut antibacterial response

“…PGN is a glycan polymer composed of alternating residues of β (1,4)-linked N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) that are cross-linked by short peptide bridges, the exact composition of which is dependent on the bacterial species and growth conditions. 4 , 6 During bacterial proliferation, up to 50% of the PGN is degraded by a turnover process that generates structurally diverse PGN fragments, called muropeptides. 7 Their recognition by PRRs belonging to various classes of proteins, such as nod-like receptors (NLRs) and peptidoglycan recognition proteins (PGRPs) in animals and lysine-motif (Lys-M) in plants, is necessary to mobilize host antibacterial defenses, but also to support developmental processes or activate behavior, to name a few.…”