bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytotoxic T‐cell responses to Mycobacterium bovis during experimental infection of cattle with bovine tuberculosis
Authors: Skinner Margot A. , Parlane Natalie , McCarthy Allison , Buddle Bryce M. 
Published: September 2003

SummaryCytotoxic T‐cell responses are thought to play a significant role in the host defence against mycobacterial infections. Little is understood about such responses of cattle to Mycobacterium bovis, the causative agent of bovine tuberculosis. The work described in this report demonstrates the activity of cytotoxic cells during experimental infection of cattle with M. bovis. The cytotoxic cells were found to have the ability to specifically lyse macrophages infected with M. bovis and were detected in peripheral blood lymphocytes after in vitro re‐exposure to M. bovis. Cytotoxic activity was detected 4 weeks after experimental infection with M. bovis; a similar level of activity was maintained during the infection and it was mediated by both WC1+γδ and CD8+ T cells. In addition, inhibition of the growth of M. bovis within infected macrophages was detected when they were exposed to cultures containing M. bovis‐specific cytotoxic cells. The ability to detect cytotoxic cells after infection of cattle with M. bovis will allow their activity to be measured during vaccination trials. Correlation of cytotoxic activity with disease outcome may aid in the design of new vaccines and vaccination strategies.
Induction of a protective capsular polysaccharide antibody response to a multiepitope DNA vaccine encoding a peptide mimic of meningococcal serogroup C capsular polysaccharide
Authors: Prinz Deborah M. , Smithson S. Louise , Kieber‐Emmons Thomas , Westerink M. A. Julie 
Published: September 2003

SummarySystemic infection by encapsulated organisms, such as Neisseria meningitidis, is a major cause of morbidity and mortality worldwide, especially in individuals less than 2 years of age. Antibodies directed at the capsular polysaccharide are shown to be protective against disease by inducing complement‐dependent bactericidal activity. The current polysaccharide vaccine has been shown to be poorly immunogenic in high‐risk groups and this is probably related to its T‐independent properties. An alternative approach to eliciting a T‐dependent serum immunoglobulin G (IgG) antibody response to encapsulated pathogens is DNA vaccination. We assessed the immunogenicity of a multiepitope DNA vaccine encoding a T‐cell helper epitope and a peptide mimic of N. meningitidis serogroup C. The DNA construct induced a significant anti‐polysaccharide antibody response that was bactericidal. Mice immunized with the DNA construct were subsequently protected against challenge with a lethal dose of N. meningitidis serogroup C.
Decay‐accelerating factor induction by tumour necrosis factor‐α, through a phosphatidylinositol‐3 kinase and protein kinase C‐dependent pathway, protects murine vascular endothelial cells against complement deposition
Authors: Ahmad Saifur R. , Lidington Elaine A. , Ohta Rieko , Okada Noriko , Robson Michael G. , Davies Kevin A. , Leitges Michael , Harris Claire L. , Haskard Dorian O. , Mason Justin C. 
Published: September 2003

SummaryWe have shown that human endothelial cells (EC) are protected against complement‐mediated injury by the inducible expression of decay‐accelerating factor (DAF). To understand further the importance of DAF regulation, we characterized EC DAF expression on murine EC in vitro and in vivo using a model of glomerulonephritis. Flow cytometry using the monoclonal antibody (mAb) Riko‐3 [binds transmembrane‐ and glycosylphosphatidylinositol (GPI)‐anchored DAF], mAb Riko‐4 (binds GPI‐anchored DAF) and reverse transcription–polymerase chain reaction (RT–PCR), demonstrated that murine EC DAF is GPI‐anchored. Tumour necrosis factor‐α (TNF‐α) increased EC DAF expression, detectable at 6 hr and maximal at 24–48 hr poststimulation. DAF upregulation required increased steady‐state DAF mRNA and protein synthesis. In contrast, no increased expression of the murine complement receptor‐related protein‐Y (Crry) was seen with TNF‐α. DAF upregulation was mediated via a protein kinase C (PKC)α, phosphoinositide‐3 kinase (PI‐3 kinase), p38 mitogen‐activated protein kinase (MAPK) and nuclear factor‐κB (NF‐κB)‐dependent pathway. The increased DAF was functionally relevant, resulting in a marked reduction in C3 deposition following complement activation. In a nephrotoxic nephritis model, DAF expression on glomerular capillaries was significantly increased 2 hr after the induction of disease. The demonstration of DAF upregulation above constitutive levels suggests that this may be important in the maintenance of vascular integrity during inflammation, when the risk of complement‐mediated injury is increased. The mouse represents a suitable model for the study of novel therapeutic approaches by which vascular endothelium may be conditioned against complement‐mediated injury.
Retinoid‐ and carotenoid‐enriched diets influence the ontogenesis of the immune system in mice
Authors: Garcia Ada L. , Rühl Ralph , Herz Udo , Koebnick Corinna , Schweigert Florian J. , Worm Margitta 
Published: September 2003

SummaryVitamin A (VA) has been identified as an important factor for the development of the immune system, especially during ontogenesis. It has been shown that antibody secretion and proliferation of lymphocyte populations depend on retinoids. In the present study we investigated the influence of a base VA diet and diets enriched with VA, β‐carotene and lycopene, on the ontogenesis of the immune system in mice. We examined the absolute and relative concentrations of splenic B lymphocytes (CD45R/B220), T lymphocytes (CD3+) and their subpopulations (CD4+ and CD8+), and measured serum immunoglobulin G (IgG) concentrations in the offspring of supplemented dams at different ages (1, 3, 5, 7, 14, 21 and 65 days). The experimental diets resulted in higher numbers of T and B lymphocytes after VA and carotenoid enrichment, when compared, at various time‐points, with the base diet. Higher values of total serum IgG were found in the β‐carotene‐enriched diet group on day 7. On days 7 and 14, the enriched diets induced significant alterations in the percentages and total numbers of splenic lymphocytes in comparison to the base diet. Our results confirm that supplementation with VA and carotenoids affect the immune‐cell function during ontogenesis and suggest a possible role of these nutritional factors on the development of the immune system.
The MHC class I antigen presentation pathway: strategies for viral immune evasion
Authors: Hewitt Eric W. 
Published: September 2003

SummaryPresumably because of the selective pressure exerted by the immune system, many viruses have evolved proteins that interfere with antigen presentation by major histocompatibility complex (MHC) class I molecules. These viruses utilize a whole variety of ingenious strategies to inhibit the MHC class I pathway. Viral proteins have been characterized that exploit bottlenecks in the MHC class I pathway, such as peptide translocation by the transporter associated with antigen processing. Alternatively, viral proteins can cause the degradation or mislocalization of MHC class I molecules. This is often achieved by the subversion of the host cell's own protein degradation and trafficking pathways. As a consequence elucidation of how these viral proteins act to subvert host cell function will continue to give important insights not only into virus–host interactions but also the function and mechanism of cellular pathways.
Heterogeneity and immunogenicity of theTrichinellaTSL‐1 antigen gp53
Authors: Romarís F. , Dea‐Ayuela M. A. , Bolás F. , Martínez‐Fernández A. R. , Sanmartín M. L. , Ubeira F. M. 
Published: September 2003

SUMMARYThis study investigates the heterogeneity and immunogenicity of theTrichinellaTSL‐1 antigen gp53. Western blotting analysis of severalTrichinellaisolates with the gp53‐specific monoclonal antibodies (mAbs) US5 and US9, produced in Btkxidmice, revealed that gp53 from the speciesT. britovi, T. murrelli andgenotype T8 had higher MW (60 kDa) than gp53 fromT. spiralis, T. nelsoni andgenotype T6 (53 kDa) and fromT. nativa(55 kDa). mAb US5 reacted only with gp53 fromT. spiralis.Experiments including immunoassays of gp53 binding by sera fromT. spiralis‐infected mice, in the presence of different potential inhibitors (recombinant gp53, US5,T. britovi‐crude larval extract (CLE), and CLEN‐ andO‐glycans), indicate (i) that gp53 fromT. spiralisbears specific epitopes that induce antibody formation during infection; (ii) that the protein epitopes of gp53 are much more important (76 or 68% of total antibody reactivity in BALB/c and Swiss CD‐1 mice, respectively) than the corresponding glycan epitopes including tyvelose (11 or 32% of total reactivity) for the induction of anti‐gp53 circulating antibodies; and (iii) that the species‐specific epitopes present on gp53 are differentially recognized in different mouse strains. Whereas in BALB/c mice US5‐ and non‐US5‐recognized species‐specific epitopes on gp53 bind about 84% of circulating antibodies on day 80 post‐infection, this percentage was only 38% in Swiss CD‐1 mice. These data on the antigenicity of gp53 contrast with data forTrichinellaCLE antigens, in that most circulating antibodies reactive with CLE antigens recognized tyvelose‐containing epitopes (57% and 58% of circulating antibodies in BALB/c and Swiss CD‐1 mice, respectively). Together these results demonstrate that gp53 is recognized during infection but is antigenically different from otherTrichinellaTSL‐1 antigens.
Serum IgG3 to the Plasmodium falciparum merozoite surface protein 2 is strongly associated with a reduced prospective risk of malaria
Authors: Metzger Wolfram G. , Okenu Daniel M. N. , Cavanagh David R. , Robinson Jane V. , Bojang Kalifa A. , Weiss Helen A. , McBride Jana S. , Greenwood Brian M. , Conway David J. 
Published: September 2003

SUMMARY The merozoite surface protein 2 (MSP2) of Plasmodium falciparum is recognized by human antibodies elicited during natural infections, and may be a target of protective immunity. In this prospective study, serum IgG antibodies to MSP2 were determined in a cohort of 329 Gambian children immediately before the annual malaria transmission season, and the incidence of clinical malaria in the following 5 months was monitored. Three recombinant MSP2 antigens were used, representing each of the two major allelic serogroups and a conserved region. The prevalence of serum IgG to each antigen correlated positively with age and with the presence of parasitaemia at the time of sampling. These antibodies were associated with a reduced subsequent incidence of clinical malaria during the follow‐up. This trend was seen for both IgG1 and IgG3, although the statistical significance was greater for IgG3, the most common subclass against MSP2. After adjusting for potentially confounding effects of age and pre‐season parasitaemia, IgG3 reactivities against each of the major serogroups of MSP2 remained significantly associated with a lower prospective risk of clinical malaria. Individuals who had IgG3 reactivity to both of the MSP2 serogroup antigens had an even more significantly reduced risk. Importantly, this effect remained significant after adjusting for a simultaneous strong protective association of antibodies to another antigen (MSP1 block 2) which itself remained highly significant.
Metalloendopeptidases from the intestinal brush border of Haemonchus contortus as protective antigens for sheep
Authors: Smith W. D. , Newlands G. F. J. , Smith S. K. , Pettit D. , Skuce P. J. 
Published: September 2003

SUMMARY Substantial protection against the economically important nematode Haemonchus contortus has been achieved by immunizing sheep with a glycoprotein fraction isolated from the intestinal membranes of this parasite. This fraction has been termed Haemonchus galactose‐containing glycoprotein complex (H‐gal‐GP) since it was originally isolated through its selective binding to lectins with a specificity for N‐acetylgalactosamine. A major component of this highly protective antigen complex is a family of four zinc metalloendopeptidases, designated MEPs 1–4. Various combinations of these MEPs were evaluated in immunization–challenge trials in sheep. In two experiments a combination of all four MEPs, separated from the rest of the complex by gel filtration in 8 m urea, significantly reduced H. contortus egg counts by 45 and 50%, an effect not significantly different from that conferred by 8 m urea treatment of H‐gal‐GP itself. Similarly, MEP3 alone or MEPs 1, 2 and 4 in combination, electroeluted from the complex following SDS gel electrophoresis, each reduced egg counts by some 33%. The MEPs are therefore protective components of H‐gal‐GP and from previously published findings, it appears that MEP3 is the most effective member of this metalloendopeptidase family. However, there was no significant protection when sheep were immunized with fully reduced and denatured H‐gal‐GP or with bacterially expressed recombinant forms of MEP 1 or the principal domains of MEP3, suggesting that conformational epitopes on the MEPs are required for immunity.
Regulatory effects of IL‐12 and IL‐18 on Onchocerca volvulus‐ and Entamoeba histolytica‐specific cellular reactivity and cytokine profiles
Authors: Pfaff Alexander W. , Kirch Astrid K. , Hoffmann Wolfgang H. , Banla Meba , Schulz‐Key Hartwig , Geiger Stefan M. , Soboslay Peter T. 
Published: September 2003

SUMMARY In the present study, the cytokines interleukin (IL)‐12 and IL‐18 were evaluated for their capacity to modulate and to re‐direct in vitro parasite antigen‐specific cellular responsiveness in patients exposed to Onchocerca volvulus and Entamoeba histolytica infection. We found that IL‐18 was highly capable of reducing parasite antigen‐induced IL‐10 production by PBMC. In contrast, addition or neutralization of IL‐12, also in combination with IL‐18 and the interferon‐γ‐inducible chemokine IP‐10 did not affect IL‐10 production. Interestingly, the highest IL‐10 levels were measured when IL‐18 and IP‐10 were both neutralized. Although having no effect on IL‐10, IL‐12 strongly promoted spontaneous and parasite antigen‐driven IFN‐γ production by PBMC, whereas IL‐18 was only moderately affecting IFN‐γ release by PBMC re‐stimulated with E. histolytica‐ or O. volvulus‐specific antigens. Both IL‐12 and IL‐18 diminished the cellular production of IL‐13, and a synergistic effect was observed when the cytokines were combined. Likewise, neutralization of IL‐12 enhanced Entamoeba and Onchocerca antigen‐driven IL‐13 production, but no further increase of IL‐13 was observed, when anti‐IL‐12 and anti‐IL‐18 were used together. This study disclosed that IL‐18 will significantly down‐regulate parasite‐specific IL‐10 production, whereas IL‐12 induced IFN‐γ and inhibited IL‐13 production by PBMC from humans exposed to O. volvulus and E. histolytica. Such selective immune‐regulatory capacity of IL‐12 and IL‐18 may comprise an important tool to re‐direct polarized cytokine responses towards a balanced Th1/Th2 cytokine profile, which may prevent pathology and promote immunity against helminth and protozoan parasite infections.
Cellular and serological responses in resistant and susceptible mice exposed to repeated infection with Heligmosomoides polygyrus bakeri
Authors: Behnke Jerzy M. , Lowe Anna , Clifford Simon , Wakelin Derek 
Published: September 2003

SUMMARY An experiment was carried out to compare the parasitological and immunological responses of SWR and CBA mice to trickle (repeated) infection with Heligmosomoides polygyrus. Male mice were given 125 L3 once per week and were killed in groups, together with naïve control mice, weekly until week 8. Worm burdens accumulated in CBA, stabilizing in week 5 in excess of 400 worms and remaining high until week 8. In contrast in SWR worm burdens peaked in week 3 at a mean worm burden of 129 and then fell sharply so that by week 6, despite continuing re‐infection, no more worms were recovered from these mice. SWR mice showed a marked mast cell and mMCP‐1 response, peaking in weeks 2–3, whereas in CBA mice these responses were slower, and even at their height in week 8 still less intense than those in SWR mice. Both strains responded initially with a very similar goblet cell response, which declined in SWR mice as worms were eliminated, but was sustained in CBA mice until week 8. Serum TNFα concentrations were higher in SWR mice throughout the experiment. Infection elicited strong serological responses against adult and L4 antigens in both SWR and CBA mice, involving all the isotypes tested (IgG1, IgA and IgE). Anti‐L3 responses were examined only for IgG1. However, only two responses differed significantly between the strains: the IgE response to L4 antigens was more intense in SWR mice, and interestingly and unexpectedly, the IgG1 response to adult worm antigens was more intense in CBA mice. These results reflect the activation of predominantly Th2‐driven effector mechanisms, that may be associated with host‐protective immunity developing under the trickle infection protocol exploited in these experiments.
Mapping of chromosomal regions influencing immunological responses to gastrointestinal nematode infections in mice
Authors: Menge David M. , Behnke Jerzy M. , Lowe Anna , Gibson John P. , Iraqi Fuad A. , Baker R. Leyden , Wakelin Derek 
Published: September 2003

SUMMARY This paper reports the results of a genome‐wide search for quantitative trait loci (QTL) influencing immunological responses to infection with the gastro‐intestinal nematode parasite Heligmosomoides polygyrus in an F2 population created by crossing the resistant SWR and the susceptible CBA inbred mouse strains. Following infections, intestinal granuloma score at post mortem, mucosal mast cell protease 1, and IgE and IgG1 titres were recorded. The susceptible CBA mice had significantly higher IgG1, but significantly lower IgE, mucosal mast cell protease 1 and granuloma scores than SWR mice. Significant QTL were mapped to chromosomes 4, 11, 13 and 17 for granuloma score; chromosomes 12 and 17 for IgE; chromosome 10, 17 and 18 for IgG1 and chromosomes 1, 9, 10, 11, 17 and 18 for mucosal mast cell protease 1. Chromosomes 10, 11, 17 and 18 had QTL affecting more than one trait, and these are most likely to represent single QTL with multiple effects rather than multiple QTL. Some of these QTL map to regions known to harbour genes responsible for the induction of immunological responses to intestinal worms.
Long‐term effects of mineral versus organic fertilizers on activity and structure of the methanotrophic community in agricultural soils
Authors: Seghers Dave , Top Eva M. , Reheul Dirk , Bulcke Robert , Boeckx Pascal , Verstraete Willy , Siciliano Steven D. 
Published: September 2003

SummaryAgricultural practices, such as mineral nitrogen fertilization, have an impact on the soil's ability to oxidize methane, but little is known about the shifts in the methanotrophic community composition associated with these practices. Therefore, the long‐term effect of both mineral (NH4NO3) and organic (manure and GFT‐compost) fertilizer applications on the soil methanotrophic community activity and structure were investigated. Both high and low affinity methane oxidation rates were lower in the soil treated with mineral fertilizer compared to the other soils. An enhanced nitrate concentration was observed in the mineral fertilized soil but nitrate did not show a direct affect on the high affinity methane oxidation. In contrast, the low affinity methane oxidation was slowed down by increased nitrate concentrations, which suggests a direct effect of nitrate on low affinity methane oxidation. Denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA gene fragments specific for methanotrophs revealed a distinct community between the mineral and organic fertilized soils as extra Type I methanotrophic bands (phylotypes) became visible in the organic fertilized soils. These phylotypes were not visible in the patterns of the added organic fertilizers suggesting an indirect effect of the organic fertilizers on the methanotrophic community. Additionally, a molecular analysis was performed after the low affinity methane oxidation test. The enhanced methane concentrations used in the test enriched certain low affinity methanotrophs in the organic fertilized soils but not in the mineral fertilized soil. Supporting the molecular and functional observations, fatty acids characteristic for methanotrophs were less abundant in the soil treated with mineral fertilizer compared to the soil treated with compost. In conclusion, the function and molecular and chemical composition of the methanotrophic community are all altered in soil fertilized with mineral fertilizer.
Effect of integration of a GFP reporter gene on fitness of Ralstonia eutropha during growth with 2,4‐dichlorophenoxyacetic acid
Authors: Füchslin Hans Peter , Rüegg Irene , Van Der Meer Jan Roelof , Egli Thomas 
Published: September 2003

SummaryGreen fluorescent proteins (GFPs) are frequently used as marker and reporter systems to assess the fate and activity of microbial strains with the ability to degrade xenobiotic compounds. To evaluate the potential of this tool for tracking herbicide‐degrading microorganisms in the environment a promoterless gfp was linked to the tfd C promoter, which is activated during degradation of the herbicide 2,4‐dichlorophenoxyacetic acid (2,4‐D), and integrated into the chromosome of the 2,4‐D–degrading strain Ralstonia eutropha JMP 134. The effects of the inserted gfp gene on the kinetics of 2,4‐D degradation by R. eutropha in batch and chemostat culture were compared to those of the wild‐type strain. In batch culture with 2,4‐D as the only carbon and energy source the maximum specific growth rate of the gfp‐marked strain did not differ significantly from the wild type. However, compared to the wild type, the 2,4‐D steady‐state concentration in 2,4‐D‐limited chemostat cultures of the gfp‐marked strain was higher at all dilution rates tested. The reduced competitiveness of the gfp‐marked strain at low substrate concentrations was confirmed in a competition experiment for 2,4‐D in continuous culture at a dilution rate of 0.075 h−1. Reproducibly, the gfp‐marked strain was displaced by the wild‐type strain. The study clearly demonstrates that fitness of constructs cannot be assessed by measuring µmax with selected substrates in batch cultures only but that a thorough kinetic analysis is needed, which also considers slow, carbon‐limited growth conditions as they occur in the environment.