Peptidoglycan and Lipoteichoic Acid in Gram-Positive Bacterial Sepsis: Receptors, Signal Transduction, Biological Effects, and Synergism

Abstract

In sepsis and multiple organ dysfunction syndrome (MODS) caused by gram-negative bacteria, lipopolysaccharide (LPS) initiates the early signaling events leading to the deleterious inflammatory response. However, it has become clear that LPS can not reproduce all of the clinical features of sepsis, which emphasize the roles of other contributing factors. Gram-positive bacteria, which lack LPS, are today responsible for a substantial part of the incidents of sepsis with MODS. The major wall components of gram-positive bacteria, peptidoglycan and lipoteichoic acid, are thought to contribute to the development of sepsis and MODS. In this review, the literature underlying our current understanding of how peptidoglycan and lipoteichoic acid activate inflammatory responses will be presented, with a focus on recent advances in this field.

Recombinant human Hsp70 protects against lipoteichoic acid-induced inflammation manifestations at the cellular and organismal levels

“…Furthermore, there is a tendency toward increased mortality in patients with Gram-positive sepsis and decreased mortality in patients infected with Gram-negative bacteria (Geerdes et al 1992). Importantly, increased drug resistance has been reported for Gram-positive bacteria, such as Staphylococcus aureus (Wang et al 2003;Leaver et al 2008).…”

Structural Basis of Recognition of Pathogen-associated Molecular Patterns and Inhibition of Proinflammatory Cytokines by Camel Peptidoglycan Recognition Protein

“…They participate in the pathogenesis of sepsis (18) by producing copious amounts of TNF-␣ and IL-6 predominantly in macrophages and T cells (19,20). The levels of TNF-␣ were increased by ϳ3.5-fold ( Fig.…”

Bacterial pathogenesis and mediators in apical periodontitis

“…LTA is a polymer of glycerol phosphate covalently attached to a glycolipid in the cytoplasmic membrane and protruding through the peptidoglycan layer. LTA can activate macrophages/monocytes and induce the release of pro-inflammatory cytokines, such as IL-1β, IL-6, CXCL8 and TNF-α (10,46). LTA exerts its effects by signaling via TLR-2 (47).…”

“…Peptidoglycan may induce diverse biological effects (45), which may play a role in the pathogenesis of apical periodontitis lesions. These effects include activation of macrophages/ monocytes with consequent release of pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF, and activation of the complement system via the alternative pathway (10,45,46). Signalling of peptidoglycan is mediated mainly through TLR-2 (47).…”