Marine algal polysaccharides: a new option for immune stimulation


Published on

Nowadays, all animal production is concerned with vaccination. This is an essential technique for the protection of livestock health which, however, entails significant costs for stock breeders. Maximizing the efficiency and profitability of prophylactic vaccination strategies is therefore a major stake. To achieve this, new avenues are constantly explored. One of these concerns is the use of new molecules extracted from seaweeds to help optimize the stimulation of the natural defences of the body and its response to vaccination strategies.

Published in: Technology, Business
  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Marine algal polysaccharides: a new option for immune stimulation

  1. 1. September | October 2013 Marine algal polysaccharides: a new option for immune stimulation The International magazine for the aquaculture feed industry International Aquafeed is published six times a year by Perendale Publishers Ltd of the United Kingdom. All data is published in good faith, based on information received, and while every care is taken to prevent inaccuracies, the publishers accept no liability for any errors or omissions or for the consequences of action taken on the basis of information published. ©Copyright 2013 Perendale Publishers Ltd.All rights reserved.No part of this publication may be reproduced in any form or by any means without prior permission of the copyright owner. Printed by Perendale Publishers Ltd. ISSN: 1464-0058 INCORPORATING f ish farming technolog y
  2. 2. Innovations for a better world. Bühler AG, Feed & Biomass, CH-9240 Uzwil, Switzerland, T +41 71 955 11 11, F +41 71 955 28 96, Fatten up your bottom line. Bühler high-performance animal and aqua feed production systems are used by leading companies around the world. These producers know they can rely not just on the technology itself, but also on the support that accompanies it. A service combining local presence with global expertise both lowers feed mill operating costs and increases capacity utilization. To find out more, visit
  3. 3. N owadays, all animal production is concerned with vaccination. This is an essential technique for the protection of livestock health which, however, entails significant costs for stock breeders. Maximizing the efficiency and profitability of prophylactic vaccination strategies is therefore a major stake. To achieve this, new avenues are constantly explored. One of these concerns is the use of new molecules extracted from seaweeds to help optimize the stimulation of the natural defences of the body and its response to vaccination strategies. Innate immunity The body’s response to the aggression of a pathogen is based on two types of immunity. They are the innate immune response and the adaptive response. The innate response is the first line of defence against pathogens. It is activated immediately and acts very quickly. This immune response can be found in all ani- mals. It will be the same whenever the body encounters that pathogen. However, the body does not retain a memory of the infectious agent. The mechanism of action of this type of immunity consists in recognizing the molecular patterns shared by numerous pathogens, which are essentially represented by membrane fractions (glycocalyx). The various elements that contribute to the innate immune response are the following: • Physical barrier (mucous membrane, skin, mucus, villi etc) • Phagocytic cells, such as the macrophages • Natural killer (NK) cells • Certain cytokines, which deliver signals warning the body of a danger • Complement system • Toll-like receptors (TLR), a family of membrane receptors only discovered recently. They control the expression of molecules that fight against infectious agents (directly or indirectly, via effector cells, and by recruiting the activation of the adaptive immune system). The elements associated with the innate immune response can act on the pathogen directly or indirectly, by producing effector cells (cytokines etc). The latter will subse- quently trigger the adaptive immunity by activating the T and B cells. Adaptive immunity Unlike the innate response, the acquired or adaptive response occurs in vertebrates only. During the first encounter with a given patho- gen (primary infection), it acts as the body’s second line of defence. Its activation takes some time - known as latency. However, this response system memorizes the pathogens it encounters and when the body is again exposed to them the latency is much shorter and the immune system reacts to the aggres- sion almost immediately. Adaptive immunity is specific: it recognises the molecular patterns of the already encountered pathogens. The various elements that contribute to the adaptive immune response are the fol- lowing: • T cells • B cells • Antibodies • Ig, TCR, CTL, antibody (AB)-producing plasma cells + coupled aid of the innate immunity effectors Seaweeds: a new source of active elements to stimulate the immune system In recent years more and more publica- tions have brought to the forefront the relevance of seaweeds in numerous biological applications, particularly to immune mecha- nisms, taking special interest in some of their components, namely the sulfated polysac- Marine algal polysaccharides: a new option for immune stimulation 18 | InternatIOnal AquAFeed | September-October 2013 FEATURE NK : Natural Killer PRR : Pattern Recognition Receptor CMH : Complexe Majeur d’histocompatibilité TCP : T Cell Receptor
  4. 4. charides. These are complex carbohydrates which do not occur in terrestrial plants. They are supposed to influence the immune system by a vast number of still poorly understood pathways. Polysaccharides represent a structurally diverse class of macromolecules which are relatively widespread in nature. There are simple and complex forms of polysachharides. Unlike proteins and nucleic acids, polysac- charides contain repetitive structural features which are chains of monosaccharide residues joined together by glycosidic bonds. Thus, they form polymer (-type) structures represented in the form of chains that may be homogenous (homopolysaccharides) or not (heteropolysaccharides). The simple forms are the homopolysac- charides composed of a single type of sugar, linked in an essentially linear manner (starch, glycogen, cellulose for example). They are essentially structural compounds or mecha- nisms of energy storage in an easily releasable form. Their structure may become more complex owing to their capacity to establish links at various levels of each elementary unit, allowing thus the development of branching structures in the three dimensions. These are the branched heteropolysaccharides. Structural variability and biological potentialities The nucleotides in nucleic acids and the amino acids in proteins can inter- connect in only one way, while the monosaccharide units in oligosaccha- rides and polysaccharides can intercon- nect at several points to form a wide variety of linear or branched structures (Sharon and Lis 1993). For instance, the number of possible permutations for four different sugar monomers can attain September-October 2013 | InternatIOnal AquAFeed | 19 FEATURE Amylose (chain of alpha-1,4 glucose) Anta® Phyt NEW: Anta® Phyt Aqua – naturally an alternative for aquaculture feeds. Feed Green! For innovative animal nutrition we now provide a purely plant based solution. Anta® Phyt Aqua: Fine-tuned for the requirements of our aquaculture thanks to the future oriented technology by Dr. Eckel, which was awarded the Aquafeed Innovation Award in Silver. > Natural > Palatable > Prebiotic > Gentle on rescources Order information now! We are happy to advise you. Aquafeed Innovation Award VICTAM Asia 2012 Silver Anta® Phyt Aqua A Anta® Phyt AntaPhyt_90x132_2.indd 1 29.07.13 10:59 Innate immunity / acquired immunity: two complementary and cooperative systems Innate immunity adaptive or acquired immunity Chronology Primary infection Quick response: first barrier against pathogens Second line of defence : latency (about 7 days) repeated infections Identical to the primary response Immune memory => latency close to zero Specificity non-specific response Specific response (Ig and tCr) recognized molecular patterns Invariable and common to numerous pathogens Specific to the infectious agent Cellular and molecular effectors Complement, phagocytic cells and certain cytokines Ctl (cytotoxic t cells) and anti- body producing plasma cells, with the help of innate effectors tCr : t Cell receptor - Ig : Immuno Globulin - Ctl : Cytotoxic t lymphocyte or Killer t cells Providing proficient tools to achieve cost-effective and sustainable aquaculture practices Central Office and Orders Jesús Aprendiz, 19. 1º A-B 28007 Madrid T. +34 915 014 041 Aqua Range AQUANOX
  5. 5. REAL BREWERS’YEAST “Made inGermany” For Leiber`s specialty yeast products, “Made in Germany”is a seal of quality. Multibiotic effect of Leiber yeast - vitality, health and performance for fish. Leiber GmbH · Hafenstraße 24, 49565 Bramsche, Germany · Tel +49 (0) 5461 9303-0 · Fax +49 (0) 5461 9303-28 · · THE SPECIAL WORLD OF LEIBER YEAST...
  6. 6. up to 35,560 unique tetrasaccharides, while four amino acids can form only 24 different permutations (Hodgson 1991). This explains the fact that, among macro- molecules, polysaccharides provide the high- est capacity for carrying biological informa- tion, as they have the greatest potential for structural variability. In addition, one of the particularities that numerous marine polysac- charides possess is their polyanionic character, which confers them a high chemical reactivity. Of these anionic polysaccharides, the majority of those which occur macroalgae are sulfated polysaccharides: galactan (agar, carraghenans), ulvans, fucans. The ulvans, for example, the water-soluble polysaccharides found in green seaweed of the order Ulvales (Ulva and Enteromorpha), have sulfate, rhamnose, xylose and iduronic and glucuronic acids as their main constitu- ents (Lahaye and Ray 1996) (Percival and McDowell 1967). Ulvan structure shows great complexity and variability as evidenced by the numerous oligosaccharide repeating structural patterns identified (Lahaye and Robic 2007). The main repeating disaccharide units reported are of ulvanobiouronic acid 3-sulfate type, containing either glucuronic or iduronic acid. In addition, a few repeating patterns can be found that contain sulfated xylose replacing uronic acid or glucuronic acid on the O-2 binding/link of the rhamnose-3-sulfate units (Lahaye and Ray 1996) (Lahaye et al. 1997). Interests This huge variability in the polysaccharide structure provides the flexibility required for exact regulatory mechanisms in different cell- cell interactions in higher organisms. Sulfation in particular seems to be con- ducive to various biological activities noted in polysaccharides extracted from marine macroalgae. Marine sulfated polysaccharides: their role and effect on immunity Sulfated polysaccharides, which are wide- spread in macroalgae, have been shown to possess anti-infectious (Cumashi et al. 2007) (Witvrouw and De Clercq 1997) (anti- viral, anti-bacterial, anti-tumoral), antioxidant (Wang et al. 2010) (de Souza et al. 2007) and anti-thrombotic (Mao et al. 2006) activities, as well as immune-modulating (Leiro et al. 2007) activities that might find relevance in stimulating the immune response or in con- trolling the activity of immune cells in order to mitigate negative effects such as inflammation (Chen et al. 2008) One of the pathways of marine sulfated polysaccharides, which has been emphasized recently, is their role in the activation of TLR. Indeed, more and more studies are demon- strating that marine algal polysaccharides can influ- ence the innate immune response by binding to recognition receptors called Pattern Recognition Receptorsc (PRR), such as the mannose recep- tors or TLRs of phagocytic cells, including and especially macrophages (Chen et al. 2008). TLRs are transmembrane proteins which detect invad- ing pathogens by binding to ancestral molecules of microbial origin called Pathogen-Associated Molecular Patterns (PAMPs). The PAMPs contact at TRL level triggers a cascade of responses resulting in the expres- sion of inflammatory response genes. In mam- mals, these recently identified receptors have been numbered from 1 to 11 (TLR1-TLR11). On contact with their respective PAMPs, TLR specifically acti- vate a signaling path- way leading to the activation of NF-kB (Nuclear Factor- kappa B) and AP1 (ActivatorProtein 1) transcription fac- tors regulating the expression of inflam- matory cytokines such as TNFα, IL-1 or IL-6. It therefore now 20 | InternatIOnal AquAFeed | September-October 2013 FEATURE Structure of the 4 main repeating ulvan patterns of Ulva lactuca Ulvanobiouronic acid A. [→ 4)-β-D- GlcA-(1 → 4)-α-L-Rha3S-(1 →] n; Ulvanobiouronic acid B. [→ 4) - α-L- IdoA-(1 → 4)-α-L-Rha3S-(1 →] n Ulvanobiose A. [→ 4)-β-D- Xyl -(1 → 4)-α-L-Rha3S-(1 →] n; Ulvanobiose B. [→ 4)-β-D- Xyl 2S-(1 → 4)-α-L-Rha3S-(1 →] n; Classification of Marine Sulfated Polysaccharides (MSP) Branched sulfated heteropolysaccharide
  7. 7. appears that TLR play a key role in the adaptive immune response, but the signals produced by their activation lead to the activation of numerous other cells and func- tions of the immune system, which makes them essential elements of both the innate immune mechanisms and of adaptive immu- nity. The activity of some sulfated algal polysac- charides as TLR activating agents might be the result of a certain structural similarity between these marine polysaccharides and bacterial lipopolysaccharides (LPS). Bacterial LPSs are indeed a type of structure occurring at the surface of their external membrane and recognized as bacteria-specific recognition elements. In particular, bacterial LPS in mam- mals are shown to be specifically recognised by TLR4. Possible applications in animal health In conclusion, seaweeds appear to contain sugars in the form of polysaccharides, some of which - sulfated polysaccharides - are complex polyanionic structures which possess various biological properties. A vast number of studies have already evidenced the effects of some of these sulfated polysaccharides, particularly the fucoidans, the carraghenans and the ulvans, on certain mechanisms of inflammatory response and on immunity. The identification and selection of these polysaccharides extracted from suitable macroalgae makes it possible to envisage the use of these molecules as agents for the stimulation of the various mechanisms associated with the body defence and, in particular, of the innate immunity mecha- nisms. Within the framework of the potential applications in the fields of animal breeding and animal health two non-exclusive strategies can be proposed: Regular sequential intakes for a general stimulation of the body’s state of defence: • With a regular intake not connected with vaccination, they allow the strengthen- ing of the body’s state of defence. Repeated use allows the development of a ‘basic’ immune sys- tem and the boosting of the state of defence of the innate system. The use of polysaccha- rides upstream or downstream of a prophylactic programme may be an asset in enhancing the level of immune protection of an individual or group of indi- viduals within a livestock and in contributing to a better control of the infectious pressure on the livestock, preventing the appearance of recurrent infec- tious pathologies. Targeted intakes within the framework of a vaccination pro- gramme: • As part of a vaccination pro- gramme, they would enhance the vaccine protection. This would definitely provide the pos- sibility to improve the intake and persistence of the vaccine and there- by to improve the technical and economic per- formance of vac- cine prophylactic programmes. More InforMatIon: September-october 2013 | InternatIonal AquAFeed | 21 FEATURE Sulfated polysaccharide Cytokine/Chemokine production
  8. 8. LINKS • See the full issue • Visit the International Aquafeed website • Contact the International Aquafeed Team • Subscribe to International Aquafeed The potential of microalgae meals – in compound feeds for aquaculture Understanding ammonia in aquaculture ponds Volume 16 Issue 5 2013 - sePTemBeR | oCToBeR INCORPORATING fIsh fARmING TeChNOlOGy EXPERT TOPIC – Salmon AquaNor event review Thisdigitalre-printispartoftheSeptember|October2013editionofInternational Aquafeed magazine. Content from the magazine is available to view free-of-charge, both as a full online magazine on our website, and as an archive of individual features on the docstoc website. Please click here to view our other publications on To purchase a paper copy of the magazine, or to subscribe to the paper edition please contact our Circulation and Subscriptions Manager on the link above. INFORMATION FOR ADVERTISERS - CLICK HERE