bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudomonas fluorescens
Encodes the Crohn's Disease-Associated I2 Sequence and T-Cell Superantigen
Authors: Wei Bo , Huang Tiffany , Dalwadi Harnisha , Sutton Christopher L. , Bruckner David , Braun Jonathan 
Published: November 2002

ABSTRACT

Commensal bacteria have emerged as an important disease factor in human Crohn's disease (CD) and murine inflammatory bowel disease (IBD) models. We recently isolated I2, a novel gene segment of microbial origin that is associated with human CD and that encodes a T-cell superantigen. To identify the I2 microorganism, BLAST analysis was used to identify a microbial homologue, PA2885, a novel open reading frame (ORF) in the
Pseudomonas aeruginosa
genome. PCR and Southern analysis identified
Pseudomonas fluorescens
as the originating species of I2, with homologues detectable in 3 of 13 other
Pseudomonas
species. Genomic cloning disclosed a locus containing the full-length I2 gene (
pfiT
) and three other orthologous genes, including a homologue of the
pbrA/pvdS
iron response gene. CD4
+
T-cell responses to recombinant proteins were potent for I2 and
pfiT
, but modest for PA2885.
pfiT
has several features of a virulence factor: association with an iron-response locus, restricted species distribution, and T-cell superantigen bioactivity. These findings suggest roles for
pfiT
and
P. fluorescens
in the pathogenesis of Crohn's disease.
A Glycoconjugate Vaccine forNeisseria meningitidisInduces Antibodies in Human Infants That Afford Protection against Meningococcal Bacteremia in a Neonate Rat Challenge Model
Authors: Mountzouros Kenneth T. , Belanger Kelly A. , Howell Alan P. , Bixler, Garvin S. , Madore Dace V. 
Published: November 2002

ABSTRACTThe functional activities of serum samples from human infants immunized with a glycoconjugate vaccine forNeisseria meningitidisserogroup C were assessed in a complement-mediated antibody-dependent serum bactericidal assay (SBA) and in a neonate rat model of protection from bacteremia. Selective serum samples from individual human infants were combined to make a panel of 11 serum pools to obtain a sufficient volume for testing. Each pool was assayed (i) for the anti-N. meningitidisserogroup C capsular polysaccharide (PS) immunoglobulin G (IgG) concentration as determined by reactivity in a direct-binding enzyme-linked immunosorbent assay, (ii) for bactericidal activity againstN. meningitidisserogroup C strain C11, and (iii) for the ability to reduce bacteremia after passive transfer into a neonate rat model. Representative serum samples from infants who were not previously immunized with anyN. meningitidisserogroup C vaccine served as a negative control. The prepared serum pools ranged in antibody concentration from 0.18 to 17.31 μg of IgG specific forN. meningitidisserogroup C PS per ml. For this serum panel, a direct relationship between concentrations of anti-N. meningitidisserogroup C PS-specific IgG and serum SBA titers (r= 0.9960) was observed. Passive transfer to neonate rats demonstrated the ability of postimmunization serum samples to significantly reduce (≥2-log10reduction compared to control animals) the level of bacteremia following a challenge. Of 79 neonate rats that received ≥0.031 μg of human infant anti-N. meningitidisserogroup C PS IgG, 75 (94.9%) had a ≥2-log10reduction in bacteremia, whereas of the animals that received <0.031 μg of antigen-specific IgG, 10.3% (4 of 39 rats) showed a ≥2-log10reduction in bacteremia. It was concluded that the anti-N. meningitidisserogroup C PS IgG antibody induced by this glycoconjugate vaccine had in vitro functional activity (as determined by a SBA) and also afforded protection against meningococcal bacteremia in an animal model.
Development of Interleukin-12-Producing Capacity throughout Childhood
Authors: Upham John W. , Lee Peter T. , Holt Barbara J. , Heaton Tricia , Prescott Susan L. , Sharp Mary J. , Sly Peter D. , Holt Patrick G. 
Published: November 2002

ABSTRACTIncreasing evidence indicates that the capacity to induce protective Th1 immune responses is impaired in early childhood, an observation that can be partially attributed to deficiencies in antigen-presenting-cell function. Synthesis of interleukin 12 (IL-12), a key Th1-trophic cytokine, is markedly reduced in the neonatal period, though there is a paucity of knowledge concerning the ontogeny of IL-12-synthetic capacity throughout the childhood years. Hence, we examined the production of bioactive IL-12 p70 by circulating mononuclear cells in a population of healthy individuals. As expected, the capacity to synthesize IL-12 p70 in response to either lipopolysaccharide or heat-killedStaphylococcus aureuswas markedly impaired at birth, even after priming of cells with gamma interferon. Surprisingly however, IL-12 p70 synthesis by peripheral blood mononuclear cells from both 5- and 12-year-old children was still substantially below that seen in adults, and this did not appear to be related to excessive production of IL-10. In contrast, dendritic cells from adults and neonates, derived from monocytes with granulocyte-macrophage colony-stimulating factor and IL-4, synthesized equivalent amounts of IL-12 p70 in response to microbial stimulation. This indicates that the impaired capacity for IL-12 synthesis in childhood is not an intrinsic property of circulating mononuclear cells but rather can be readily overcome in response to appropriate maturational stimuli. Because IL-12 arose predominantly from circulating HLA-DR+cells that lacked B-cell- and monocyte-specific markers, we propose that the slow maturation of IL-12-synthetic capacity in the childhood years can be attributed to deficiencies in the number and/or function of dendritic cells.
Antimonial Therapy Induces Circulating Proinflammatory Cytokines in Patients with Cutaneous Leishmaniasis
Authors: Kocyigit Abdurrahim , Gur Selahaddin , Gurel Mehmet S. , Bulut Vedat , Ulukanligil Mustafa 
Published: November 2002

ABSTRACTThe objective of this study was to evaluate the association between antimonial therapy and circulating levels of proinflammatory cytokines in patients with cutaneous leishmaniasis (CL). Patients were treated with conventional chemotherapy by using pentavalent antimonium salts (Glucantime) for 3 weeks. Circulating plasma levels of the proinflammatory cytokines interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) were determined for CL patients and healthy subjects before and 3 weeks after the treatment was started. Plasma IL-1β, IL-6, IL-8, and TNF-α levels were significantly higher for pretreatment CL patients than for healthy subjects. Proinflammatory cytokines significantly increased after 21 days postinfection compared to levels for the pretreatment patients. These increments were approximately 3-fold for IL-1β and TNF-α levels, 10-fold for IL-6 levels, and 20-fold for IL-8 levels in patients with CL. Taken together these results indicate that circulating proinflammatory cytokine levels were increased in patients with CL as a consequence of host defense strategies, and antimonial therapy may induce these cytokines by affecting the macrophage or other components of the host defense system.
Role of β-d-Galactofuranose inLeishmania majorMacrophage Invasion
Authors: Suzuki Erika , Tanaka Ameria K. , Toledo Marcos S. , Takahashi Helio K. , Straus Anita H. 
Published: November 2002

ABSTRACTThe role of glycosylinositol phospholipid 1 (GIPL-1) ofLeishmania(Leishmania)majorin the interaction of promastigotes and amastigotes with macrophages was analyzed. Monoclonal antibody MEST-1, which recognizes glycolipids containing terminal galactofuranose (Galf) residues (E. Suzuki, M. S. Toledo, H. K. Takahashi, and A. H. Straus, Glycobiology7:463-468, 1997), was used to detect GIPL-1 inLeishmaniaby indirect immunofluorescence and to analyze its role in macrophage infectivity.L. majorpromastigotes showed intense fluorescence with MEST-1, and GIPL-1 was detected in both amastigote and promastigote forms by high-performance thin-layer chromatography immunostaining by using MEST-1. Delipidation ofL. majorpromastigotes with isopropanol-hexane-water eliminated the MEST-1 reactivity, confirming that only GIPL-1 is recognized in either amastigotes or promastigotes of this species. The biological role of GIPL-1 in the ability ofL. majorto invade macrophages was studied by using either Fab fragments of MEST-1 or methylglycosides. Preincubation of parasites with Fab fragments reduced macrophage infectivity in about 80% of the promastigotes and 30% of the amastigotes. Preincubation of peritoneal macrophages withp-nitrophenyl-β-galactofuranoside (10 mM) led to significant (∼80%) inhibition of promastigote infectivity. These data suggest that a putative new receptor recognizing β-d-Galf is associated withL. majormacrophage infectivity and that GIPL-1 containing a terminal Galf residue is involved in theL. major-macrophage interaction.
Leishmania pifanoiPathogenesis: Selective Lack of a Local Cutaneous Response in the Absence of Circulating Antibody
Authors: Colmenares María , Constant Stephanie L. , Kima Peter E. , McMahon-Pratt Diane 
Published: November 2002

ABSTRACTRecently, a role for B cells in the pathogenesis associated with infection byLeishmania(Leishmania mexicanacomplex andL. donovani) has been established. In the case ofL. mexicanacomplex parasites (L. mexicana,L. pifanoi, andL. amazonensis), a critical role for immunoglobulin G-mediated mechanisms for the amastigote stage in the host is evident; however, the immunological mechanisms involved remain to be established. In vitro analysis of the kinetics of parasite uptake by macrophages failed to indicate a major effect of antibody opsonization. Given the importance of CD4+T cells in the development of disease caused by these parasites, the possibility that the lack of pathogenesis was due to the lack of development of an immune response at the local site (draining lymph node and/or cutaneous site) was explored. Interestingly, the level of CD4+-T-cell activation (proliferation and cytokine) in draining lymph nodes from mice lacking circulating antibody (resistant) was found to be comparable to that in nodes from wild-type mice (susceptible) at 2, 5, and 10 weeks postinfection. However, antibody-deficient animals had markedly reduced numbers of monocytes and lymphocytes recruited or retained at the site of cutaneous infection in comparison to wild-type mice, indicating a selective impairment in the local cutaneous immune response. In vitro antigen presentation studies employing tissue-derived (opsonized) amastigotes demonstrated thatL. pifanoi-infected FcR−/−macrophages, in contrast to comparably infected wild-type cells, failed to activateLeishmaniaantigen-specific T lymphocytes. These data, taken together, suggest that one possible mechanism for the role of antibody in pathogenesis may be to mediate parasite uptake and regulate the immune response at the local cutaneous site of infection.
Immunization with a Combination of Merozoite Surface Proteins 4/5 and 1 Enhances Protection against Lethal Challenge withPlasmodium yoelii
Authors: Kedzierski Lukasz , Black Casilda G. , Goschnick Matthew W. , Stowers Anthony W. , Coppel Ross L. 
Published: November 2002

ABSTRACTIt is widely believed that subunit vaccines composed of multiple components will offer greater protection against challenge by malaria, and yet there is little experimental evidence to support this view. We set out to test this proposition in thePlasmodium yoeliichallenge system in rodents by comparing the degree of protection conferred by immunization with a mixture of merozoite surface proteins to that conferred by single proteins. We therefore examined a defined protein mixture made of the epidermal growth factor-like domains ofP. yoellimerozoite surface protein 1 (MSP1) and MSP4/5, the homologue ofP. falciparumMSP4 and MSP5. In the present study we demonstrate that this combination of recombinant proteins dramatically enhances protection against lethal malaria challenge compared to either protein administered alone. Many mice immunized with the MSP4/5 plus MSP119combination did not develop detectable parasitemia after challenge. Combined immunization with MSP119and yMSP4/5, a product characterized by lower protective efficacy, also greatly enhanced protection by reducing peak parasitemias and increasing the numbers of survivors. In some combination trials, levels of antibodies to MSP119were elevated compared to the MSP119alone group; however, improved protection occurred regardless of whether boosting of the anti-MSP119response was observed. Boosting of anti-MSP119did not appear to be due to contaminating endotoxin in the EcMSP4/5 material since enhanced protection was observed in C3H/HeJ mice, which are endotoxin insensitive. Collectively, these experiments show that multiantigen combinations offer enhanced levels of protection against asexual stage infection and suggest that combinations of MSP1, MSP4, and MSP5 should be evaluated further for use in humans.
Dynamics of Gamma Interferon, Interleukin-12 (IL-12), IL-10, and Transforming Growth Factor β mRNA Expression in PrimaryMycobacterium bovisBCG Infection in Guinea Pigs Measured by a Real-Time Fluorogenic Reverse Transcription-PCR Assay
Authors: Kawahara Mamoru , Nakasone Tadashi , Honda Mitsuo 
Published: November 2002

ABSTRACTThe guinea pig has been utilized as a model for studying infectious diseases because its reactions closely resemble those of humans biologically and immunologically. However, the cytokine responses in this animal remain to be studied. Initially, we established a quantitative assay using a real-time reverse transcription-PCR (RT-PCR) to measure guinea pig gamma interferon (IFN-γ), interleukin-12 (IL-12), IL-10, and transforming growth factor β (TGF-β) mRNA. By preparing primer-fluorogenic probe sets for these cytokines and standard RNA templates corresponding to the target sequence of each cytokine, we obtained linear standard curves essential for quantitative determination. In guinea pigs immunized by intradermal (i.d.) vaccination with the Tokyo strain ofMycobacterium bovisBCG (0.1 mg) or else hyperimmunized with the same vaccine (10 mg) given intravenously (i.v.), peripheral blood mononuclear cells (PBMCs) at 4 weeks showed an increase in IFN-γ mRNA expression in the latter but not the former animals. However, at week 10, IFN-γ mRNA expression was markedly elevated in PBMCs, spleen cells, and cells in bronchoalveolar lavage fluid in both the i.d.- and the i.v.-immunized animals, the level of expression being 10 times higher in the latter. In contrast, the expression levels of IL-12 mRNA in PBMCs, spleen cells, and BAL cells were not enhanced in either group at 10 weeks postimmunization. The expression of IL-10 and TGF-β increased slightly only in PBMCs. Regardless of differences in the levels of cytokine responses, the magnitudes of the purified protein derivative of tuberculin-specific delayed-type hypersensitivity (DTH) skin reactions for the two groups did not differ significantly at 8 weeks postvaccination. In this study, we quantitatively measured IL-10, IL-12, TGF-β, and IFN-γ mRNA in BCG-immunized guinea pigs and showed that the level of IFN-γ mRNA expression does not necessarily reflect the magnitude of the DTH response, suggesting that there may be an intricate relationship between protective immunity, the level of IFN-γ, and the DTH response. Thus, our quantitative assay would be of use for the development of vaccines using guinea pig models.
Mannoprotein fromCryptococcus neoformansPromotes T-Helper Type 1 Anticandidal Responses in Mice
Authors: Pietrella Donatella , Mazzolla Rosanna , Lupo Patrizia , Pitzurra Lucia , Gomez Maria Jesus , Cherniak Robert , Vecchiarelli Anna 
Published: November 2002

ABSTRACTWe previously demonstrated that mannoprotein (MP) fromCryptococcus neoformans(CnMP) stimulates interleukin-12 production by human monocytes, thus fostering a T-helper type 1 (Th1) protective anticryptococcal response. In this paper we show that CnMP was also able to induce aCandida albicans-directed protective Th1 response. This was demonstrated for mice immunized with CnMP by induction of a delayed-type hypersensitivity (DTH) reaction toC. albicansMP (CaMP) as well as induction of gamma interferon production by CD4+and CD8+splenic T cells stimulated in vitro with CaMP. CnMP-immunized mice were also partially protected from lethal systemic challenge withC. albicans, as shown by prolonged median survival times and decreased fungal burden in the kidney. Much evidence supports the validity of these cross-reactive and functional Th1 responses: (i) a non-cross-reactiveC. albicansantigen, such as enolase, did not produce a DTH response to CaMP; (ii) passive adoptive transfer of T cells primed with CnMP induced a DTH reaction; (iii)C. neoformansextract elicited a DTH response to CaMP; and (iv) a monoclonal antibody (7H6) directed against a major and immunodominant T-cell-stimulatory 65-kDa MP (MP65) ofC. albicansalso recognized discrete 100-kDa constituents ofC. neoformansextracts, as well as secretory constituents of the fungus. These results suggest the presence of common Th1 antigenic determinants in the mannoproteic material ofC. neoformansandC. albicansepitopes, which should be considered in devising common strategies for immunoprophylactic or immunotherapeutic control of the fungi.
Anomalous Role of Tumor Necrosis Factor Alpha in Experimental Enterococcal Infection
Authors: Papasian Christopher J. , Silverstein Richard , Gao Jian Jun , Bamberger David M. , Morrison David C. 
Published: November 2002

ABSTRACTThe murined-galactosamine (d-gal) model of tumor necrosis factor alpha (TNF-α) hypersensitization was used as an initial tool to investigate the potential contribution of TNF-α to lethal intraperitoneal (i.p.) infection withEnterococcus faecalis.d-gal sensitized mice to lethalE. faecalisinfection, whereas dexamethasone and neutralizing anti-TNF-α antibody protectedd-gal-treated,E. faecalis-infected mice, implicating TNF-α in the lethal response toE. faecalisinfection ind-gal-treated mice. Circulating TNF-α was undetectable for at least 8 h following i.p.E. faecalisinfection, although low peritoneal levels of TNF-α were detected within 3 h, suggesting that localized TNF-α production contributed to the lethal response toE. faecalisinfection ind-gal-treated mice. Although i.p.E. faecalisinfection failed to induce a detectable systemic TNF-α response, circulating Interleukin-6 (IL-6) was detected within 3 h of infection. IL-6 was also detected in the peritoneum within an hour of infection, prior to the appearance of peritoneal TNF-α. In striking contrast to in vivo results,E. faecalisinduced a potent and rapid TNF-α response from both mouse peritoneal macrophages and the RAW 264.7 cell line in vitro. This led us to hypothesize that TNF-α production in response toE. faecalisinfection is suppressed by IL-6 in vivo. In vitro experiments demonstrated a statistically significant, but modest, inhibitory effect of IL-6 on TNF-α production by RAW cells stimulated withE. faecalis. Collectively, these data indicate that acute, lethalE. faecalisinfection appears to induce an unusual cytokine response that differs in character from that previously described for most other gram-positive and gram-negative bacteria.
Differences in Expression of Toll-Like Receptors and Their Reactivities in Dendritic Cells in BALB/c and C57BL/6 Mice
Authors: Liu Tie , Matsuguchi Tetsuya , Tsuboi Naotake , Yajima Toshiki , Yoshikai Yasunobu 
Published: November 2002

ABSTRACTWe have previously reported that differences in early production of interleukin 12 (IL-12) by dendritic cells (DC) underlies the difference between the susceptibilities toListeria monocytogenesof C57BL/6 and BALB/c mice. To elucidate mechanisms for the different abilities of DC to produce cytokine in C57BL/6 and BALB/c mice, we examined Toll-like receptor (TLR) expression by DC and their responses in vitro to known microbial ligands for TLRs. We found that DC isolated from the spleens of naive C57BL/6 mice preferentially expressed TLR9 mRNA, whereas DC from naive BALB/c mice strongly expressed TLR2, -4, -5, and -6 mRNAs. C57BL/6 DC produced a higher level of IL-12p40 in response to the ligands for TLR4 (lipopolysaccharide), TLR2 (lipoprotein), and TLR9 (CpG), whereas BALB/c DC responded to these ligands by producing a larger amount of monocyte chemoattractant protein 1. C57BL/6 DC expressed higher levels of CD40 and Stat4 than BALB/c DC did, suggesting that naive C57BL/6 mice contained more-mature subsets of DC than naive BALB/c mice. Differences in reactivities of DC to microbial molecules through TLRs may be associated with susceptibility and resistance toListeriainfection in BALB/c and C57BL/6 mice.
EndoS and SpeB fromStreptococcus pyogenesInhibit Immunoglobulin-Mediated Opsonophagocytosis
Authors: Collin Mattias , Svensson Mikael D. , Sjöholm Anders G. , Jensenius Jens C. , Sjöbring Ulf , Olsén Arne 
Published: November 2002

ABSTRACTThe human pathogenStreptococcus pyogenesprimarily infects the upper respiratory tract and skin, but occasionally it disseminates and causes severe invasive disease with high mortality. This study revealed that the activity of extracellular EndoS, which hydrolyzes the functionally important N-linked oligosaccharides on opsonizing immunoglobulin G (IgG), contributes to increased survival ofS. pyogenesin human blood ex vivo. The inability to kill the bacteria is due to reduced binding of IgG to Fc receptors and impaired classical pathway-mediated activation of complement. In addition, the activity of extracellular SpeB, which cleaves IgG into Fc and Fab fragments, also increases bacterial survival. This suggests thatS. pyogenesexpresses two enzymes, EndoS and SpeB, which modulate IgG by different mechanisms in order to evade the adaptive immune system.
Marked Enhancement of the Antigen-Specific Immune Response by Combining Plasmid DNA-Based Immunization with a Schiff Base-Forming Drug
Authors: Charo Jehad , Sundbäck Maria , Wasserman Ken , Ciupitu Anne-Marie T. , Mirzai Babak , van der Zee Ruurd , Kiessling Rolf 
Published: November 2002

ABSTRACTAlthough plasmid DNA (pDNA)-based immunization has proven efficacy, the level of immune responses that is achieved by this route of vaccination is often lower than that induced by traditional vaccines, especially for primates and humans. We report here a simple and potent method to enhance pDNA-based vaccination by using two different plasmids encoding viral or bacterial antigens. This method is based on coadministration of low concentrations of a recently described immunopotentiating, Schiff base-forming drug called tucaresol which has led to significant augmentation of antigen-specific humoral and cellular immune responses. Our data suggest that enhancement of the immune response with tucaresol might provide a powerful tool for the further development of pDNA-based immunization for humans.