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Marine algal polysaccharides: a new option for immune stimulation

Marine algal polysaccharides: a new option for immune stimulation

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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.
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.

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I N C O R P O R AT I N G f i s h far m ing t e c h no l og y

September | October 2013 Marine algal polysaccharides: a new option for immune stimulation

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

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FEATURE

Marine algal polysaccharides: a new option for immune stimulation

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.

defence against pathogens. It is activated immediately and acts very quickly. This immune response can be found in all animals. 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 subsequently 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 pathogen (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 aggression 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 following: • T cells • B cells • Antibodies • Ig, TCR, CTL, antibody (AB)-producing plasma cells + coupled aid of the innate immunity effectors

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

Seaweeds: a new source of active elements to stimulate the immune system
In recent years more and more publications have brought to the forefront the relevance of seaweeds in numerous biological applications, particularly to immune mechanisms, taking special interest in some of their components, namely the sulfated polysac-

NK : Natural Killer PRR : Pattern Recognition Receptor CMH : Complexe Majeur d’histocompatibilité TCP : T Cell Receptor

18 | InternatIOnal AquAFeed | September-October 2013

FEATURE
Innate immunity / acquired immunity: two complementary and cooperative systems Innate immunity Quick response: first barrier against pathogens Identical to the primary response non-specific response Invariable and common to numerous pathogens adaptive or acquired immunity Second line of defence : latency (about 7 days) Immune memory => latency close to zero Specific response (Ig and tCr) Specific to the infectious agent

Primary infection Chronology repeated infections Specificity

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 interconnect in only one way, while the Ctl (cytotoxic t cells) and antiComplement, phagocytic monosaccharide units in oligosacchaCellular and molecular effectors body producing plasma cells, cells and certain cytokines rides and polysaccharides can interconwith the help of innate effectors nect at several points to form a wide tCr : t Cell receptor - Ig : Immuno Globulin - Ctl : Cytotoxic t lymphocyte or Killer t cells variety of linear or branched structures (Sharon and Lis 1993). For instance, homogenous (homopolysaccharides) or not the number of possible permutations for charides. These are complex carbohydrates which do not occur in terrestrial plants. They (heteropolysaccharides). The simple forms four different sugar monomers can attain are supposed to influence the immune system are the homopolysacby a vast number of still poorly understood charides composed of a single type of sugar, pathways. Amylose (chain of Polysaccharides represent a structurally linked in an essentially alpha-1,4 glucose) diverse class of macromolecules which are linear manner (starch, relatively widespread in nature. There are glycogen, cellulose for simple and complex forms of polysachharides. example). They are Unlike proteins and nucleic acids, polysac- essentially structural charides contain repetitive structural features compounds or mechawhich are chains of monosaccharide residues nisms of energy storage in an easily releasable joined together by glycosidic bonds. Thus, they form polymer (-type) structures form. Their structure represented in the form of chains that may be may become more
recognized molecular patterns

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FEATURE 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).

Branched sulfated heteropolysaccharide

Interests
This huge variability in the polysaccharide structure provides the flexibility required for exact regulatory mechanisms in different cellcell interactions in higher organisms. Sulfation in particular seems to be conducive to various biological activities noted in polysaccharides extracted from marine macroalgae.

Marine sulfated polysaccharides: their role and effect on immunity
Sulfated polysaccharides, which are widespread in macroalgae, have been shown to possess anti-infectious (Cumashi et al. 2007) (Witvrouw and De Clercq 1997) (antiviral, 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 controlling 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 demonThe ulvans, for example, the water-soluble strating that marine algal polysaccharides can influpolysaccharides found in green seaweed of ence the innate immune response by binding to the order Ulvales (Ulva and Enteromorpha), recognition receptors called Pattern Recognition have sulfate, rhamnose, xylose and iduronic Receptorsc (PRR), such as the mannose recepand glucuronic acids as their main constitu- tors or TLRs of phagocytic cells, including and ents (Lahaye and Ray 1996) (Percival and especially macrophages (Chen et al. 2008). TLRs are transmembrane proteins which detect invadMcDowell 1967). Ulvan structure shows great complexity ing pathogens by binding to ancestral molecules and variability as evidenced by the numerous of microbial origin called Pathogen-Associated oligosaccharide repeating structural patterns Molecular Patterns (PAMPs). The PAMPs contact at TRL level triggers a identified (Lahaye and Robic 2007). The main repeating disaccharide units reported are of cascade of responses resulting in the expresulvanobiouronic acid 3-sulfate type, containing sion of inflammatory response genes. In mameither glucuronic or iduronic acid. In addition, mals, these recently identified receptors have a few repeating patterns can be found that been numbered from 1 to 11 (TLR1-TLR11). On contact with their respective PAMPs, TLR specifically actiClassification of Marine Sulfated Polysaccharides (MSP) vate a signaling pathway leading to the Structure of the 4 main repeating ulvan activation of NF-kB patterns of Ulva lactuca (Nuclear FactorUlvanobiouronic acid A. [→ 4)-β-Dkappa B) and AP1 GlcA-(1 → 4)-α-L-Rha3S-(1 →] n; (ActivatorProtein Ulvanobiouronic acid B. [→ 4) - α-L1) transcription facIdoA-(1 → 4)-α-L-Rha3S-(1 →] n tors regulating the Ulvanobiose A. [→ 4)-β-D- Xyl -(1 → expression of inflam4)-α-L-Rha3S-(1 →] n; matory cytokines Ulvanobiose B. [→ 4)-β-D- Xyl 2S-(1 → such as TNFα, IL-1 4)-α-L-Rha3S-(1 →] n; or IL-6. It therefore now

up to 35,560 unique tetrasaccharides, while four amino acids can form only 24 different permutations (Hodgson 1991). This explains the fact that, among macromolecules, polysaccharides provide the highest capacity for carrying biological information, as they have the greatest potential for structural variability. In addition, one of the particularities that numerous marine polysaccharides 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.

20 | InternatIOnal AquAFeed | September-October 2013

FEATURE strengthening of the body’s state of defence. Repeated use allows the development Sulfated of a ‘basic’ polysaccharide immune system and the boosting of the state of defence of the innate system. The use of polysaccharides upstream appears that TLR play a key role in the or downstream adaptive immune response, but the signals of a prophylactic produced by their activation lead to the programme may activation of numerous other cells and funcbe an asset in tions of the immune system, which makes enhancing the them essential elements of both the innate level of immune immune mechanisms and of adaptive immuprotection of nity. an individual or The activity of some sulfated algal polysacgroup of indicharides as TLR activating agents might be viduals within a the result of a certain structural similarity livestock and in between these marine polysaccharides and contributing to bacterial lipopolysaccharides (LPS). Bacterial a better control LPSs are indeed a type of structure occurring of the infectious at the surface of their external membrane pressure on and recognized as bacteria-specific recognition the livestock, elements. In particular, bacterial LPS in mampreventing the mals are shown to be specifically recognised appearance of by TLR4. recurrent infectious pathologies. Possible applications Targeted intakes in animal health within the framework In conclusion, seaweeds appear to contain sugars in the form of polysaccharides, some of of a vaccination prowhich - sulfated polysaccharides - are complex gramme: • As part of a polyanionic structures which possess various vaccination probiological properties. A vast number of studies gramme, they have already evidenced the effects of some of would enhance these sulfated polysaccharides, particularly the the vaccine fucoidans, the carraghenans and the ulvans, on protection. This certain mechanisms of inflammatory response would definitely and on immunity. provide the posThe identification and selection of these sibility to improve polysaccharides extracted from suitable the intake and macroalgae makes it possible to envisage persistence of the the use of these molecules as agents for vaccine and therethe stimulation of the various mechanisms by to improve associated with the body defence and, in the technical and particular, of the innate immunity mechaeconomic pernisms. formance of vacWithin the framework of the potential cine prophylactic applications in the fields of animal breeding programmes. and animal health two non-exclusive strategies can be proposed: Regular sequential intakes for a general stimulation of the body’s state of defence: More InforMatIon: • With a regular intake not connected Website: www.olmix.com with vaccination, they allow the
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September-october 2013 | InternatIonal AquAFeed | 21

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