AquacultureResearch, 2010, 41, 356^372                                     doi: 10.1111/j.1365-2109.2009.02374.x
                 Nutrition and immunity: an update
                 VivianeVerlhacTrichet
                 ResearchCentreofAnimalNutritionandHealth,NRD/CA^DSMNutritionalProductsFrance,Saint-LouisCedex,France
                 Correspondence:V VerlhacTrichet Research Centre of Animal Nutrition and Health, NRD/CA^DSM Nutritional Products France, BP
                 170,68305Saint-Louis Cedex, France. E-mail: viviane.verlhac@dsm.com
                 Abstract                                                Mostrecentreviewsonthetopicofnutritionandim-
                 Immunity encompasses all mechanisms and re-             munity or, more generally, health are from Lall
                 sponsesusedbytheorganismtodefenditselfagainst           (2000)andVerlhacandViswanath(2004).
                 bacteria, viruses or parasites. Adequate supply and       The¢rstsectionreviews¢shandshrimpimmunity,
                 balanceofnutrientsarerequiredforpropere⁄ciency          comparing innate and adaptive immune mechan-
                 of the host defences. Research has identi¢ed dietary    isms, highlighting the importance of innate immu-
                 factors that a¡ect human and animal immune re-          nity in those animals.The second section highlights
                 sponses like amino acids, fatty acids, minerals and     the key ¢ndings in the area of nutrition and immu-
                 vitamins. Some of these nutrients have been proven      nity, analysing the relationship between immune
                 to have speci¢c actions on immunity whenprovided        responses and the di¡erent classes of nutrients, ex-
                 at pharmacological doses. This paper will review        tendingittonutraceuticalsusedasfeedadditives.
                 thesenutrientsandtheircurrentuseinaquaculture.            Thelastsectionwilldealwiththeevaluationofthe
                 The immune system is an e⁄cient but complex sys-        immuneresponsesof¢shandthemethodscurrently
                 tem. Its complexity has made the assessment of the      usedincludingcellularandmolecularapproaches,in
                 e¡ects of diets di⁄cult. Nevertheless, the standardi-   line with the study of the nutritional modulation of
                 zationof methodologyaswellastheuseofnewtech-            the immune response. Prophylaxis means and per-
                 niques at the cell or the gene level should help to     spectives are discussed inthe conclusions.
                 better understand the mechanisms of immune mod-
                 ulation.Thispaperwillreviewthemajorfunctionsof
                 ¢shandshrimpimmunesystemandthemethodolo-                Fish and shrimp immunity
                 gies used. Cellular and humoral functions including
                 cytokines will be discussed in relation to potential    Being immune corresponds to the capacityof an or-
                 means to modulate them and the underlying me-           ganismtoresist infectionthroughthe recognitionof
                 chanism.Abetterunderstandingofthemechanisms             a foreign agent, the responses of the system to ¢ght
                 of modulation of the immune functions should help       this agent and the memoryof this agent, in order to
                 in the discovery of new dietary factors to improve      quickly respond to a second aggression. In compari-
                 the immune status of the animal, leading to better      sonwith mammals, ¢sh have a less speci¢c immune
                 disease resistance.                                     system with a shorter response, a limited immuno-
                                                                         globulin repertoire, a weak memory (which reduces
                 Keywords: aquaculture, ¢sh, shrimp, nutrition,          thepotentialforlong-termprotection)andamucosal
                 immunity,modulation                                     response (whose importance incomparisonwiththe
                                                                         systemic response is not reallyknown).The immune
                                                                         response of ¢sh is di¡erentiated between humoral-
                 Introduction                                            and cellular-mediated systems, with the same type
                                                                         of immunecells suchas BandTlymphocytesacting
                 The paper intends to provide an update on the rela-     intheseresponses.
                 tionshipsbetweennutritionandimmunityofaquatic             Shrimp as invertebrates are not able to develop a
                 animals and more speci¢cally of ¢sh and shrimp.         speci¢c response. They have the basal mechanisms
                                                                                                          r2010 TheAuthors
                 356                                                             JournalCompilationr2010BlackwellPublishingLtd
                                  AquacultureResearch, 2010, 41, 356^372                              Nutritionandimmunity:anupdate VVerlhacTrichet
                                  of self- versus non-self recognition, phagocytosis and        tory response are interferon (IFN), interleukins (ILs),
                                  a systemof lectins that can be considered to be anti-         chemokines and factors like tumour-necrosis factor
                                  body-likeproteins.                                            (TNF-a). Pathogen-associated molecular patterns
                                     The response of ¢sh to a foreign agent is rather           (PAMP) of recognition have also been discovered as
                                  similar to that of mammals, while in shrimp, the re-          animportantelementof the innate immunity, invol-
                                  sponse is very rudimentary. All ¢sh pathogens con-            vingdi¡erentreceptortypes.
                                  tain antigens: viral particles, bacteria, fungi, toxins         The third line of defence consists of the develop-
                                  andanimalparasites.                                           ment of a speci¢c immune response with either the
                                                                                                proliferation of lymphocytes leading to the produc-
                                  Distinctionbetweeninnateandspeci¢c                            tionof antibodies speci¢c to the antigenor the devel-
                                  immunity                                                      opment of a T-cell-mediated response via cytotoxic
                                                                                                Tcells (e¡ectorcells) in case of viral infection, for ex-
                                  Figure 1 presents the di¡erent mechanisms involved            ample. These responses are generally also mediated
                                  intheinnateandspeci¢c(oradaptive)immunity.Fish                by cytokines, which play an important role in cell-
                                  have an important ¢rst line of defence consisting of          to-cell communication for a rapid expansion of the
                                  epithelial barriers such as skin, scales, mucus mem-          response to the di¡erent parts of the body. The ulti-
                                  branes (gastro-intestinal tract, secretions of mucus)         matestepofthisspeci¢cresponseisthedevelopment
                                  and physiological barriers like stomach pH, gut mi-           of a memory, allowing the immune system to main-
                                  cro£ora and chemical mediators secreted by the mu-            tainaB-cellpro¢lecorrespondingtoaspeci¢cpatho-
                                  cus (defensins, lysozyme, transferrin, complement             gen. In case of a second infection, these cells will be
                                  system, etc.). Involvement of cells like phagocytes,          recognizedandwillproliferatequicklyto¢ghtthein-
                                  natural cytotoxic cells (NCC) and in£ammatory re-             fection.This memory mechanism is muchless devel-
                                  sponse through the release of chemical mediators              oped in ¢sh compared with mammals and does not
                                  represents a second line of defence that is initiated if      exist in shrimp.
                                  thepathogenhasbeenabletopasstheepithelialand                    In terms of kinetics of the responses, the innate
                                  physiological barriers. The actors of the in£amma-            immunity can act between hours and days, while
                                                 Infection 
                                                                Innate immunity                           Adaptive immunity
                                                 Epithelial barriers 
                                                                                                 B lymphocytes    ->     Antibodies 
                                                 Phagocytes               
                                                                                 NC
                                                 Natural cytotoxic cells 
                                                                                     Bacteria    T lymphocytes -> Effector cells 
                                                                    Histamine 
                                                                         Phagocyte               Memory 
                                                 Inflammation: chemical mediators 
                                                                                  Time after infection: 
                                                 Hours to days                                     Days to week
                                  Figure1 Distinctionbetweeninnateandspeci¢cimmunity.AdaptedfromAbbas,LichtmannandPober(1999).
                                  r2010 TheAuthors
                                  JournalCompilationr2010BlackwellPublishingLtd, AquacultureResearch, 41,356^372                                     357
                 Nutritionandimmunity:anupdate VVerlhacTrichet                         AquacultureResearch, 2010, 41,356^372
                 the speci¢c immunity would need weeks to develop        of virus-infected cells.Through a mechanismof per-
                 depending mainly on the environment (Bowden             forin granules released externally, the membrane of
                 2008).                                                  the virus-infected cells will be degraded and subse-
                                                                         quently subjected to an osmotic shock, leading to
                                                                         theircompletelysisanddeath(Fig.3).
                 Cellularactorsof innate immunity
                 Phagocytes and NCC are the main cellular elements       Humoralfactorsofinnateimmunity
                 of the innate immunity. As shown in Fig. 2, phago-
                 cytes are able to develop di¡erent microbicidal me-     Interferon is also involved inanti-viral innate immu-
                 chanisms to try to de¢nitely eliminate pathogens.       nity (Fig. 4). Following viral infection, type I IFN is
                 Enzymes, reactive oxygen species and nitric oxide       released and recognized by speci¢c receptors on the
                 (NO) act in concert to provide the best chances to      membrane of non-infected cells. The binding of IFN
                 limit the response to the second line of defences de-   to membrane receptors initiates the secretion of en-
                 scribed earlier. The production of reactive oxygen      zymeslikelysozyme, whichwillthenblocktherepli-
                 species, either internally or externally, constitutes   cationofthevirusandwillinduceananti-viralstate.
                 the oxidative burst mechanism. The extracellular          Thein£ammatoryresponseconsistsof therelease
                 response is more pronounced in ¢sh compared with        of chemical mediators: histamine, prostaglandins
                 theintracellularone.                                    (PG), complement and cytokines (IL1b,6,8,10,
                   Natural cytotoxic cells are involved in innate anti-  12, TNF-a). Interleukin1bhas been characterized in
                 viralimmunity.Naturalcytotoxiccellspossessrecep-        teleost ¢sh (Randelli, Buonocore & Scapigliati 2008).
                 tors that recognize proteins expressed at the surface   Interleukin 6 have been identi¢ed at the molecular
                                                        Extra-cellular killing of microbes 
                                                                Microbes
                                                     Enzymes
                                                                                  ROS       NO
                                                             Extra-cellular            Extra-
                                                                                       cellular
                                  Lysosome
                                                                    Phagosome
                                                                                             NO
                                                                                    ROS       O
                                 Phagolysosome                                                  2
                                                      O         ROS
                                                        2
                                                        Intra-cellular killing of microbes 
                 Figure 2 Microbicidalmechanismsofphagocytosis.AdaptedfromAbbasetal. (1999).
                                                                                                           r2010 TheAuthors
                 358                                 JournalCompilationr2010BlackwellPublishingLtd, AquacultureResearch, 41,356^372
                                AquacultureResearch, 2010, 41, 356^372                          Nutritionandimmunity:anupdate VVerlhacTrichet
                                                                                NCC                          NCC
                                                    Virus-infected cell                               Lysis of virus-infected
                                Figure 3 Naturalcytotoxicitycells inanti-viral innate immunity. Adapted fromAbbas etal. (1999).
                                                                         Type I IFN 
                                                                                IFN  receptor 
                                                  Virus-infected cell
                                                                                            IFN induces an anti-viral state:
                                                                                            blocking viral infection of cells
                                                                                              IFN induces an anti-viral state:
                                                                                                 blocking viral replication
                                Figure 4 Interferoninanti-viralinnateimmunity.AdaptedfromAbbasetal.(1999).
                                level in sea bream by Castellana, Iliev, Sepulcre,       leading to the recruitment and activation of phago-
                                MacKenzie,Goetz,MuleroandPlanas(2008).                   cytes but they also found implications of TNF-a in
                                   Tumour necrosis factor-a is conserved in all ver-     di¡erentaspectsascomparedwithmammalslikein-
                                tebrate classes and has been identi¢ed in teleost        creasedsusceptibilitytoviralinfectionandincreased
                                                     ¤                                   virus replication.
                                ¢sh.Roca,Mulero,Lopez-munoz,Sepulcre,Renshaw,
                                                              
                                MeseguerandMulero(2008)havedemonstratedthat                 All this workoncytokinesandchemokinesis still,
                                the main proin£ammatory e¡ects of ¢sh TNF-a are          foragreatpart,carriedoutatthemolecularleveland
                                mediated through the activation of endothelial cells,    thereforethereisaneedtodemonstratethebiological
                                r2010 TheAuthors
                                JournalCompilationr2010BlackwellPublishingLtd, AquacultureResearch, 41,356^372                             359