Pectin Interaction with Immune Receptors is Modulated by Ripening Process in Papayas

Abstract

Dietary fibers have been shown to exert immune effects via interaction with pattern recognition receptors (pRR) such as toll-like receptors (tLR) and nucleotide-binding oligomerization domain (noD)like receptors. Pectin is a dietary fiber that interacts with PRR depending on its chemical structure. Papaya pectin retains different chemical structures at different ripening stages. How this influence PRR signaling is unknown. The aim of this work was to determine how ripening influences pectin structures and their ability to interact with TLR2, 3, 4, 5 and 9, and NOD1 and 2. It was evaluated the interaction of the water-soluble fractions rich in pectin extracted from unripe to ripe papayas. The pectin extracted from ripe papayas activated all the TLR and, to a lesser extent, the NOD receptors. The pectin extracted from unripe papayas also activated TLR2, 4 and 5 but inhibited the activation of TLR3 and 9. The differences in pectin structures are the higher methyl esterification and smaller galacturonan chains of pectin from ripe papayas. Our finding might lead to selection of ripening stages for tailored modulation of pRR to support or attenuate immunity. Dietary fibers (DF) commonly represent a wide variety of polysaccharides originating from fruits, vegetables, whole grains and legumes with several health benefits. Such benefits include slow gastric empty 1 and improve physical bowel function 2. Besides the physical benefits, DF can also interact directly with intestinal cells and/or the immune cells from the mucosa 3-5. It is not just the direct effects of DF on cells may trigger immune modulations 6 but also the DF fermentation in the gut 7,8. The direct interaction of DF with the intestinal cells may occur through pattern recognition receptors (PRR) 9. The PRR are germline-encoded sensors expressed in intestinal epithelial cells and gut immune cells. PRR are the key receptors responsible for the recognition of exogenous molecules by the host 5,9. Toll-like receptors (TLR) are a family of PRR that play a central role in the activation of innate immunity 10 and have been shown to be involved in DF-induced immune signaling as described below. The immune response mediated by TLR activation requires the recruitment of myeloid differentiation primary response protein 88 (MyD88) adaptor and the translocation of NF-κB to the nucleus 10. Only TLR3 NF-κB activation is not dependent on MyD88 protein which is mediated by TIR domain-containing adapter inducing IFN-β (TRIF), though 11. The interactions between wide variety of DF and TLR have been extensively studied. DF have a complex and heterogeneous structure and some DF activate TLR to different extents 12 while other DF (such as pectin) seem to block TLR signaling and attenuate intestinal inflammation 6. Nucleotide-binding oligomerization domains (NOD) have also been shown to be influenced by DF, such as β2 → 1-fructans. NOD are proteins responsible for the recognition of intracellular bacteria 10. Through this signaling via PRR, DF have been shown to mediate several ho...

An acidic polysaccharide (AGC3) isolated from North American ginseng (Panax quinquefolius) suspension culture as a potential immunomodulatory nutraceutical

“…4 E). It has been shown previously that RGI-type pectins activated the canonical NF-κB pathway through various TLRs (mainly TLR2 and 4) and MyD88 ( Prado et al., 2020 ). Prado et al.…”

“…It has been shown previously that RGI-type pectins activated the canonical NF-κB pathway through various TLRs (mainly TLR2 and 4) and MyD88 ( Prado et al., 2020 ). Prado et al. (2020) also showed that the lower molecular weight pectins were able to activate NF-κB through nucleotide-binding oligomerization domain-containing protein 2 (NOD2), and to a lesser extent, NOD1 in a dose dependent manner.…”

“…Immunomodulatory pectic RGI-type of polysaccharides have been previously isolated from plants such as Carica papaya ( Prado et al., 2020 ), Avicennia marina ( Fang and Chen, 2013 ) and Centella asiatica ( Wang et al., 2005 ). Some of these pectins have reported complement fixing, mitogenic and macrophage activating properties.…”

Panax quinquefolius (North American Ginseng) Polysaccharides as Immunomodulators: Current Research Status and Future Directions

“…Other receptors, such as complement receptor 3 (CR3), scavenger receptors (SRs), and nuclear oligomerization domain-2 (NOD-2), have been shown to bind to polysaccharides causing an immunostimulating response [ 9 , 65 , 90 , 91 ]. CR3, a member of the beta-integrins [ 92 ] is known to cause the activation of Syk, leading to the activation of phosphatidylinositol 3-kinase [ 93 ].…”

“…Different scavenger receptors, such as SCARF1 and CD36, which bind to β-glucans, have also been shown to work in conjunction with TLR2 [ 103 , 104 , 105 ]. NOD-2 is a member of the NOD—leucine rich repeat (LRR), or NOD-like receptor (NLR) family of receptors, which is known to bind peptidoglycans and can be activated by muramyl dipeptide, but has also been shown to bind partially digested polysaccharides [ 90 , 106 , 107 ]. NOD-2 then signals to RIP-2 (also known as RICK), which leads to the IKK activation through TAK1 signaling [ 107 , 108 ].…”