Sweeten PAMPs: role of sugar complexed PAMPs in innate immunity and vaccine biology

Abstract

Innate sensors play a critical role in the early innate immune responses to invading pathogens through sensing of diverse biochemical signatures also known as pathogen associated molecular patterns (PAMPs). These biochemical signatures primarily consist of a major family of biomolecules such as proteins, lipids, nitrogen bases, and sugar and its complexes, which are distinct from host molecules and exclusively expressed in pathogens and essential to their survival. The family of sensors known as pattern recognition receptors (PRRs) are germ-line encoded, evolutionarily conserved molecules, and consist of Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), C-type lectin-like receptors (CLRs), and DNA sensors. Sensing of PAMP by PRR initiates the cascade of signaling leading to the activation of transcription factors, such as NF-κB and interferon regulatory factors (IRFs), resulting in a variety of cellular responses, including the production of interferons (IFNs) and pro-inflammatory cytokines. In this review, we discuss sensing of different types of glycosylated PAMPs such as β-glucan (a polymeric sugar) or lipopolysaccharides, nucleic acid, and so on (sugar complex PAMPs) by different families of sensors, its role in pathogenesis, and its application in development of potential vaccine and vaccine adjuvants.

Immunostimulatory polysaccharide isolated from the leaves of Diospyros kaki Thumb modulate macrophage via TLR2

“…Based on these results, we suggest that PLE0 activates the TLR2/Myd88-dependent pathway as a TLR2 ligand and consequently enhances immune responses in IFN-␥-primed RAW 264.7 macrophages. It has been reported that TLR2 senses a number of polysaccharide types, such as lipoteichoic acid, teichoic acid, peptidoglycan, glycophosphatidylinositol anchored proteins, lipoarabinomannan, and arabinogalactan [49]. Unfortunately, because the characterization of glycosyl linkage in PLE0 remains to be elucidated, we could not identify the region recognized by TLR2.…”

Glycomaterials for probing host–pathogen interactions and the immune response

“…The molecular signature of pathogens, often referred to as pathogen-associated molecular patterns (PAMPs), is recognized by immune pattern recognition receptors (PRRs) on DCs. Sugar-complexed PAMPs 102 are the largest constituents of PAMPs and include lipopolysaccharide (LPS), N -acetylglucosamine (GlcNAc), peptidoglycan, and glucan-containing cell walls. Activation of PRRs results in the expression of antigen-presenting molecules (MHCII), co-stimulatory factors (CD80/86, CD40), and pro-inflammatory cytokines.…”

Co‐expression of TLR‐9 and MMP‐13 is associated with the degree of tumour differentiation in prostate cancer

“…In humans thirteen members of the Toll‐like receptors (TLR), family have been described. These are conserved membrane proteins which bind to components of bacteria, fungi and viruses as well as the damage‐associated molecular patterns (DAMPs) . Among TLRs, TLR‐9 recognizes unmethylated CpG dinucleotides expressed in bacteria and viruses and also vertebrate DNA.…”