Les nématodes gastrointestinaux (NGIs) représentent une contrainte majeure en élevage des ruminants. Jusqu’à présent, la maîtrise de ces parasitoses a reposé essentiellement sur l’emploi répété de traitements anthelminthiques (AH) de synthèse. Cependant, le développement constant de résistances aux AH dans les populations de nématodes chez les petits ruminants conduit à rechercher des méthodes alternatives ou complémentaires de lutte contre ces parasitoses. Au cours des deux dernières décennies, les données se sont accumulées montrant que certaines plantes étaient dotées de propriétés anthelminthiques, ce qui a été associé à la présence de tannins condensés (TCs) et de flavonoïdes. Ces ressources contenant des TCs, exploitées comme nutricaments, représentent donc une alternative attractive à la chimiothérapie, en combinant des effets bénéfique sur la santé et la nutrition des ruminants. Toutefois, une des difficultés à résoudre, pour un usage pertinent de ces nutricaments, est de comprendre l’origine de la variabilité des résultats observés dans l’activité AH. A côté de facteurs quantitatifs, la qualité (la structure) des TC semble également jouer un rôle dans les propriétés antiparasitaires mais ce facteur demeure peu exploré. En utilisant Haemonchus contortus comme modèle expérimental de nématode et le sainfoin (Onobrychis viciifolia) comme modèle de plantes contenant des tannins, l’objectif général de cette thèse a été de mieux comprendre les relations structure/activité des TCs. Les objectifs spécifiques des diverses études menées ont été 1) d’ examiner in vitro (par la méthode LEIA) l’activité AH de 36 fractions purifiées de TCs présentant une large diversité de caractéristiques structurelles [ex: la taille (mDP), les proportions prodelphinidols /procyanidols (PD/PC) et trans/cis ], et 2) le rôle possible d’interactions entre tannins et flavonoïdes, 3) d’ évaluer et comparer in vivo chez des agneaux, les conséquences sur les populations de vers et sur la résilience de l’hôte de la distribution de 2 ressources contenant des TCs de qualité contrastée pour les valeurs PD/PC [fort PD/PC, sainfoin (O. viciifolia); bas PD/PC, pellicules de noisettes (Corylus avellana)], 4) d’ examiner si les résultats varient en fonction de l’espèce et de la localisation des parasites (abomasum, H. contortus vs intestin grêle, Trichostrongylus colubriformis), 5) d’évaluer les concentrations, la qualité et la bio-disponibilité des TCs le long du tube digestif chez les ovins. Les résultats acquis ont montré: 1) des relations in vitro entre certaines caractéristiques des TCs et l’activité AH : un rapport élevé PD/PC pour les 2 espèces de nématodes auquel s’ajoute un rôle de la taille des tanins (mDP) pour H. contortus sont les facteurs identifiés. De manière générale, H. contortus s’est avéré plus sensible (valeurs EC50 plus faibles) aux effets des diverses ressources que T. colubriformis. Des synergies d’effets AH ont été observés entre tannins et flavonoides (quercétine et lutéoline), tout particulièrement dans le cas de TCs avec un faible rapport PD/PC. Dans l’étude in vivo, les agneaux consommant du sainfoin ont montré des effets AHs et une amélioration de la résilience de l’hôte alors que les effets de la noisette ont été beaucoup plus discrets. Les analyses menées sur les contenus des divers organes digestifs et les fèces, pour les deux types de ressources ont montré de fortes réductions de TCs détectés par rapport aux teneurs initiales dans la ration alors que les caractéristiques de structure étaient globalement préservées au long du tube digestif. En conclusion, le rôle de la qualité (structure) des TCs dans l’activité AH a été confirmé à la fois par les études in vitro et in vivo. Ces résultats suggèrent l’importance de prendre en compte ces facteurs dans la recherche de ressources pouvant être exploitées comme futurs nutricaments chez les ruminants. / Gastrointestinal nematodes (GINs) represent a major threat for the breeding and production of grazing ruminants. So far, their control has been based mainly on the repeated use of synthetic AH drugs. However, worm populations in small ruminants have consistently developed resistance against all AH drugs. In the search for alternative solutions to such drug treatments, the last two decades have provided evidence that some plants possess natural AH bioactivity. This has been related to the presence of condensed tannins (CTs) and flavonoids. Therefore, CT-containing resources represent a promising alternative to chemotherapy especially when used as nutraceuticals that combine beneficial effects on health and nutrition in small and large ruminants. However, one of the main constraint to use these nutraceuticals relates to the variations in AH results. The structural features (quality) that contribute to the AH activities of CTs remain elusive. By using the GIN Haemonchus contortus as a experimental model of nematode and Onobrychis viciifolia as a model of CT-containing plant, the general aim of this PhD was to better understand the structure/activity relationship of CT. The specific objectives were i) to examine in vitro (LEIA) the AH activity of 36 purified CT fractions with a wide range of structural features [i.e. size (mDP), prodelphinidin/procyanidin (PD/PC) and trans/cis ratios], and ii) the possible role of interactions between tannins and flavonoids, iii) to evaluate in vivo the AH activity and host resilience of two CT-resources with contrasting PD/PC ratios (i.e. high PD/PC, O. viciifolia; low PD/PC, Corylus avellana), iv) to examine whether these results vary depending on the parasites species (abomasal, H. contortus vs intestinal, Trichostrongylus colubriformis), v) to examine the CT availability (quantity and quality) along the digestive tract in sheep. In regard of CT features and AH activity, in vitro correlations were observed between AH activity and high PD/PC for both species. mDP was an additional criteria for H. contortus. Lower EC50 values were assessed for H. contortus. Synergistic AH effects were observed between CT and flavonoids (quercetin and lutein), and they were higher with fractions of low PD/PC ratios. In vivo, the lambs consuming sainfoin pellets showed consistently higher AH effects and improvement in the host’s resilience. Analyses of digesta samples and faeces, for both diets showed large reduction of detected CT related to the feed, whereas the CT structures seem preserved along the gut. In our studies, the role of CT structural features in the AH activity was observed both in vitro and in vivo. These results confirmed the influence of CT quality in the AH effects, and underline the relevance of taking these factors into account when screening CT resources as potential nutraceuticals in small ruminants.

The series of experiments described in this thesis were designed to investigate the role of suckling or late weaning in the response of young lambs to nematode infection. All experiments were conducted outdoors with grazing animals and no supplementation but for suckled groups of lambs whose counterparts were weaned to ryegrass – white clover swards. The parasite of interest was mainly Teladorsagia circumcincta solely but with mixed infection of Trichostrongylus colubriformis in one instance. In Chapter 3 (first experiment), the hypothesis that milk per se may have a direct effect on nematode development, rather than an indirect effect through enhancement of host immunity by superior nutrient supply was tested. Sixty, twinborn lambs were used, allocated to one of eight groups formed by either dosing lambs from 42 days of age or not with the equivalent of 1000 or 250 L₃ T. circumcincta larvae d⁻¹ until five days before necropsy, while a twin was either weaned at 39 days of age, suckled as single or twin until necropsy on day 84. The possibility that weaning one of a twin set onto pasture in close proximity to the ewe would cause abnormal ewe and lamb behaviour was tested by replicating the work in twins maintained as twins but in which one twin received equivalent of 250 and the other 1000 L₃ T. circumcincta larvae d⁻¹. This showed no abnormal ewe nursing or lamb suckling behaviour as a result of weaning a twin in a set. Relatively low faecal egg counts (FEC) and a two to three fold lower worm burdens suggest suckling could reduce larval establishment. Inability to detect peripheral titres of immunoglobulins supports this conclusion. An intra worm-population regulation of T. circumcincta, indicated by a pattern of greater egg-laying by a numerically smaller but physiologically better developed nematode population in suckled lambs measured in eggs 'in utero' and worm length made interpretation of FEC difficult. Suckling significantly improved weight gain and carcass weights, but early weaning did not reduce resilience to infection. In Chapter 4 (second experiment), 40 pairs of twin lambs, average age of 39 days, were either infected with the equivalent of 1000 L₃ T. circumcincta larvae d⁻¹ or not, while one twin was weaned and the other allowed to continue suckling. Necropsy was carried out on groups of five and six lambs from each of the uninfected and infected treatments, respectively, at mean age of 84, 112, and on six lambs from each group at 140 days of age. This serial slaughter allowed further confirmation of the hypothesis in Chapter 3 but also investigated the long-term effect of suckling on resistance or resilience of lambs at the trial when immune responses were anticipated to be developing. An in vitro direct larval challenge (IVDC) study, to monitor larval establishment, was carried out on tissue explants from necropsied lambs. Suckled lambs consistently showed lower FEC (P < 0.05) and worm burdens (P < 0.05) at every phase of the trial. Within the infected groups, % in vitro larval rejection suggested earlier immune responses in the weaned lambs by day 84, which was not consistent with lower worm burdens in suckled lambs but appeared similar in the subsequent necropsies. Lambs continued to show better growth due to suckling while weaning did not reduce the resilience of lambs confirming observations in Chapter 3. The immunoglobulin profile suggested the commencement of immune responses in lambs from the period after the 84th day necropsy, with significantly greater (P < 0.01) IgA titre in the infected groups, and the suckled lambs towards the end of the trial on day 140. A vaccinating effect of early exposure to parasites was coincidentally revealed as a result of unintentional pasture larval contamination, seen in suckled non-infected lambs shedding fewer eggs and harbouring fewer worms during the later necropsies compared with their weaned non-infected counterparts. In Chapter 5 (third trial), 93 pairs of twin lambs, 47 pairs of which received a vaccinating mixed infection of T. circumcincta and T. colubriformis larvae (60 L₃ / kg W / d) at ratio 40:60, respectively during the period 36 – 103 days of age, were either weaned early on day 51 or later on day 108. All lambs were drenched on day 108 and groups received challenge infections from day 116, at same rate with the vaccinating infection, or not, which ceased five days before respective necropsies. Necropsies were carried out on selected lambs on days 108, 184 and 218. The direct effect of milk on larval establishment appeared to feature only in the T. circumcincta populations on slaughter day 108. The long-term benefit of late weaning for development of resistance was conditional on lambs receiving the vaccinating infection, and appeared to be more pronounced in the small intestine, reflected by a greater reduction of T. colubriformis populations in that organ than of T. circumcincta populations in the abomasum. A negative consequence of enhanced immune response was the suggestion of an increased metabolic cost in reduced performance of lambs. In conclusion, the work provides support to the hypotheses that: (a.) suckling may reduce the establishment of nematode larvae through the direct effect of milk, (b.) may enhance rapid development of host immunity to infection, and (c.) it further suggests that lack of larval experience during suckling may have long term negative implications for host resistance. Finally, it suggests that milk may play little role in the enhancement of host resilience to infection and, on the contrary, that additional metabolic cost may be associated with a more rapid development of immunity resulting from larval challenge while suckling.