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ABSTRACT: A comparative experimental study was performed between Barbados Black Belly (resistant) and INRA-401 (susceptible) breeds of sheep in which primary infection with Haemonchus contortus was terminated on day 16. Measurements of parasite burden, abomasal tissue eosinophilia, IL-4, IL-5 and IL-13 mRNA transcripts in abomasal mucosa, and in vitro larval killing abilities of blood eosinophils were performed. The results show that: (1) worm burden was significantly lower and blood eosinophilia higher in the Black Belly than in the INRA breed. (2) Abomasal cytokine expression was noticed but no difference existed between the two breeds. (3) Three out of four Black Belly sheep had higher tissue eosinophil numbers compared to the INRA sheep (more eosinophils observed in the pyloric than in the fundic region in both breeds). (4) No significant difference was observed in the in vitro larval immobilizing potential of eosinophils between the two breeds. Collectively, abomasal eosinophil number and larval killing abilities of blood eosinophils do not seem to explain the difference in worm burden between the two breeds.
Veterinary Parasitology 08/2009; 165(1-2):161-4. · 2.58 Impact Factor
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Clinical Microbiology and Infection 04/2009; 15 Suppl 2:26-7. · 4.54 Impact Factor
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F Barillet,
D Mariat,
Y Amigues,
R Faugeras,
H Caillat,
K Moazami-Goudarzi,
R Rupp,
J M Babilliot, C Lacroux,
S Lugan,
F Schelcher,
C Chartier,
F Corbière,
O Andréoletti,
C Perrin-Chauvineau
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ABSTRACT: In sheep, susceptibility to scrapie is mainly influenced by polymorphisms of the PrP gene. In goats, there are to date few data related to scrapie susceptibility association with PrP gene polymorphisms. In this study, we first investigated PrP gene polymorphisms of the French Alpine and Saanen breeds. Based on PrP gene open reading frame sequencing of artificial insemination bucks (n=404), six encoding mutations were identified at codons 127, 142, 154, 211, 222 and 240. However, only seven haplotypes could be detected: four (GIH(154)RQS, GIRQ(211)QS, GIRRK(222)S and GIRRQP(240)) derived from the wild-type allele (G(127)I(142)R(154)R(211)Q(222)S(240)) by a single-codon mutation, and two (S(127)IRRQP(240) and GM(142)RRQP(240)) by a double-codon mutation. A case-control study was then implemented in a highly affected Alpine and Saanen breed herd (90 cases/164 controls). Mutations at codon 142 (I/M), 154 (R/H), 211 (R/Q) and 222 (Q/K) were found to induce a significant degree of protection towards natural scrapie infection. Compared with the baseline homozygote wild-type genotype I(142)R(154)R(211)Q(222)/IRRQ goats, the odds of scrapie cases in IRQ(211)Q/IRRQ and IRRK(222)/IRRQ heterozygous animals were significantly lower [odds ratio (OR)=0.133, P<0.0001; and OR=0.048, P<0.0001, respectively]. The heterozygote M(142)RRQ/IRRQ genotype was only protective (OR=0.243, P=0.0186) in goats also PP(240) homozygous at codon 240. However, mutated allele frequencies in French Alpine and Saanen breeds were low (0.5-18.5 %), which prevent us from assessing the influence of all the possible genotypes in natural exposure conditions.
Journal of General Virology 03/2009; 90(Pt 3):769-76. · 3.36 Impact Factor
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G Terefe, C Lacroux,
O Andreoletti,
C Grisez,
F Prevot,
J P Bergeaud,
J Penicaud,
V Rouillon,
L Gruner,
J C Brunel,
D Francois,
J Bouix,
P Dorchies,
P Jacquiet
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ABSTRACT: The immune responses to Haemonchus contortus were compared in studies in resistant Barbados Black Belly (BBB) and susceptible INRA 401 (INRA) breeds of lambs. The cytokine patterns indicated a Th2-biased response in both breeds. A more persistent and elevated Th2 cytokine mRNA transcription and blood eosinophilia were noted in the BBB lambs. However, at days 4 and 30 post-infection, abomasal recruitment of eosinophils and mast cells were similar between the two breeds. Following primary infections, the BBB demonstrated a substantially lower faecal egg count compared to the INRA lambs. Furthermore, worm counts at 4 and 30 days post-infection, and adult female worm size and in utero egg counts 30 days after the first infection were significantly lower in the BBB than in the INRA breed. In the INRA breed, re-infection caused a significant reduction in most parasitological parameters compared with those observed after the primary infection. A similar response was not observed in the BBB sheep. In conclusion, while the major driving force in the response to H. contortus infection is a Th2-biased immunity in which the BBB showed its maximal performance during the primary infection, the INRA breed performed better after re-infection compared to its response to first exposure.
Parasite Immunology 09/2007; 29(8):415-24. · 2.60 Impact Factor
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C Lacroux,
F Corbière,
G Tabouret,
S Lugan,
P Costes,
J Mathey,
J M Delmas,
J L Weisbecker,
G Foucras,
H Cassard,
J M Elsen,
F Schelcher,
O Andréoletti
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ABSTRACT: Placentae from scrapie-affected ewes are an important source of contamination. This study confirmed that scrapie-incubating ewes bearing susceptible genotypes could produce both abnormal prion protein (PrPSc)-positive and -negative placentae, depending only on the PRP genotype of the fetus. The results also provided evidence indicating that scrapie-incubating ARR/VRQ ewes may be unable to accumulate prions in the placenta, whatever the genotype of their progeny. Multinucleated trophoblast cells appeared to play a key role in placental PrPSc accumulation. PrPSc accumulation began in syncytiotrophoblasts before disseminating to uninucleated trophoblasts. As these result from trophoblast/uterine epithelial cell fusion, syncytiotrophoblast cells expressed maternal and fetal PrPC, whilst uninucleated trophoblast cells only expressed fetal PrPC. In ARR/VRQ scrapie-infected ewes, expression of the ARR allele by syncytiotrophoblasts appeared to prevent initiation of PrPSc placental deposition. The absence of prions in affected ARR/VRQ sheep placentae reinforces strongly the interest in ARR selection for scrapie control.
Journal of General Virology 04/2007; 88(Pt 3):1056-61. · 3.36 Impact Factor
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O Andréoletti,
S Simon, C Lacroux,
N Morel,
G Tabouret,
A Chabert,
S Lugan,
F Corbière,
P Ferré,
G Foucras,
H Laude,
F Eychenne,
J Grassi,
F Schelcher
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ABSTRACT: Because variant Creutzfeldt-Jakob disease (vCJD) in humans probably results from consumption of products contaminated with tissue from animals with bovine spongiform encephalopathy, whether infectious prion protein is present in ruminant muscles is a crucial question. Here we show that experimentally and naturally scrapie-affected sheep accumulate the prion protein PrP(Sc) in a myocyte subset. In naturally infected sheep, PrP(Sc) is detectable in muscle several months before clinical disease onset. The relative amounts of PrP(Sc) suggest a 5,000-fold lower infectivity for muscle as compared to brain.
Nature Medicine 07/2004; 10(6):591-3. · 22.46 Impact Factor
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E Uro-Coste,
H. Cassard,
S Simon,
S. Lugan,
J M Bilheude,
A Perret-Liaudet,
J.E. Ironside,
S. Haik,
C. Basset-Leobon, C Lacroux,
K. Peoch,
N Streichenberger,
J.P.M. Langeveld,
M W Head,
J Grassi,
J J Hauw,
F Schelcher,
M B Delisle,
O Andreoletti
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ABSTRACT: Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability
PLoS Pathogens 4 (2008) 3.
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J.C. Espinosa,
O Andreoletti,
J Castilla,
M.E. Herva,
M Morales,
E. Alamillo,
F.D. San-Segundo, C Lacroux,
S. Lugan,
F J Salguero,
J.P.M. Langeveld,
J M Torres
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ABSTRACT: Sheep can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern. In this study, the transmission in BoPrP-Tg110 mice of prions from BSE-infected sheep was examined and compared to the transmission of original cattle BSE in cattle and sheep scrapie prions. Our results indicate no transmission barrier for sheep BSE prions to infect BoPrP-Tg110 mice, but the course of the disease is accelerated compared to the effects of the original BSE isolate. The shortened incubation period of sheep BSE in the model was conserved in subsequent passage in BoPrP-Tg110 mice, indicating that it is not related to infectious titer differences. Biochemical signature, lesion profile, and PrPSc deposition pattern of both cattle and sheep BSE were similar. In contrast, all three sheep scrapie isolates tested showed an evident transmission barrier and further adaptation in subsequent passage. Taken together, those data indicate that BSE agent can be altered by crossing a species barrier, raising concerns about the virulence of this new prion towards other species, including humans. The BoPrP-Tg110 mouse bioassay should be considered as a valuable tool for discriminating scrapie and BSE in sheep.
Journal of Virology 81 (2007) 2.
