bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-Protective Efficacy of a ProphylacticLeishmania donovaniDNA Vaccine against Visceral and Cutaneous Murine Leishmaniasis
Authors: Aguilar-Be Ingrid , da Silva Zardo Renata , Paraguai de Souza Edilma , Borja-Cabrera Gulnara Patrícia , Rosado-Vallado Miguel , Mut-Martin Mirza , del Rosario García-Miss Maria , Palatnik de Sousa Clarisa Beatriz , Dumonteil Eric 
Published: January 2005

ABSTRACTThe fucose-mannose ligand (FML) complex ofLeishmania donovaniis a promising vaccine candidate against murine and canine visceral leishmaniasis, and its main component is a 36-kDa nucleoside hydrolase (NH36). In this study, we tested the immune response and protection induced by the purified FML, the recombinant NH36 (rNH36), and NH36 DNA vaccines against the agents of visceral (L. chagasi) and cutaneous (L. mexicana) leishmaniasis in BALB/c mice. Mice developed weak humoral response to the vaccines alone, except for those immunized with FML. However, all three vaccine groups presented elevated immunoglobulin G (IgG), IgG1, and IgG2a levels after infection withL. chagasi, whereas no differences were observed between vaccine and control groups after infection withL. mexicana. A strong intradermal reaction toL. donovaniandL. mexicanaantigens was observed in mice immunized with rNH36 or FML, whereas mice immunized with NH36 DNA only reacted againstL. donovaniantigens. Experimental infection of immunized mice demonstrated that FML and rNH36 induced significant protection againstL. chagasiinfection with reductions in parasite loads of 79%. FML also conferred partial protection againstL. mexicanainfection. The best protection was observed in mice immunized with the VR1012-NH36 DNA vaccine, which induced an 88% reduction inL. chagasiparasite load and a 65% reduction inL. mexicanalesion size. Fluorescence-activated cell sorting analysis indicated the DNA vaccine induced a two- to fivefold increase in gamma interferon-producing CD4+T cells, indicating a Th1-type immune response. Our results showed that the NH36 DNA vaccine induced a strong immunoprotection against visceral and cutaneous leishmaniasis, suggesting that this DNA vaccine represents a very good candidate for use against severalLeishmaniaspecies.
Mannoproteins fromCryptococcus neoformansPromote Dendritic Cell Maturation and Activation
Authors: Pietrella Donatella , Corbucci Cristina , Perito Stefano , Bistoni Giovanni , Vecchiarelli Anna 
Published: January 2005

ABSTRACTOur previous data show that mannoproteins (MPs) fromCryptococcus neoformansare able to induce protective responses against bothC. neoformansandCandida albicans. Here we provide evidence that MPs foster maturation and activation of human dendritic cells (DCs). Maturation was evaluated by the ability of MPs to facilitate expression of costimulatory molecules such as CD40, CD86, CD83, and major histocompatibility complex classes I and II and to inhibit receptors such as CD14, CD16, and CD32. Activation of DCs was measured by the capacity of MPs to promote interleukin-12 and tumor necrosis factor alpha secretion. DC-induced maturation and interleukin-12 induction are largely mediated by engagement of mannose receptors and presume MP internalization and degradation. DC activation leads to IκBα phosphorylation, which is necessary for nuclear factor κB transmigration into the nucleus. MP-loaded DCs are efficient stimulators of T cells and show a remarkable capacity to promote CD4 and CD8 proliferation. In conclusion, we have evidenced a novel regulatory role of MPs that promotes their candidacy as a vaccine against fungi.
CpG Oligodeoxynucleotides Adsorbed onto Polylactide-Co-Glycolide Microparticles Improve the Immunogenicity and Protective Activity of the Licensed Anthrax Vaccine
Authors: Xie Hang , Gursel Ihsan , Ivins Bruce E. , Singh Manmohan , O'Hagan Derek T. , Ulmer Jeffrey B. , Klinman Dennis M. 
Published: January 2005

ABSTRACTTo reduce the biothreat posed by anthrax, efforts are under way to improve the protection afforded by vaccination. This work examines the ability of immunostimulatory CpG oligodeoxynucleotides (ODN) adsorbed onto cationic polylactide-co-glycolide (PLG) microparticles (CpG ODN-PLG) to accelerate and boost the protective immunity elicited by Anthrax Vaccine Adsorbed (AVA, the licensed human anthrax vaccine). The results indicate that coadministering CpG ODN-PLG with AVA induces a stronger and faster immunoglobulin G response against the protective antigen of anthrax than AVA alone. Immunized mice were protected from lethal anthrax challenge within 1 week of vaccination with CpG ODN-PLG plus AVA, with the level of protection correlating with serum immunoglobulin G anti-protective antigen titers.
Invariant Vα14 Chain NKT Cells PromotePlasmodium bergheiCircumsporozoite Protein-Specific Gamma Interferon- and Tumor Necrosis Factor Alpha-Producing CD8+T Cells in the Liver after Poxvirus Vaccination of Mice
Authors: Korten Simone , Anderson Richard J. , Hannan Carolyn M. , Sheu Eric G. , Sinden Robert , Gadola Stephan , Taniguchi Masaru , Hill Adrian V. S. 
Published: January 2005

ABSTRACTUnderstanding the protective mechanism in the liver induced by recombinant vaccines against the pre-erythrocytic stages of malaria is important for vaccine development. Most studies in mice have focused on splenic and peripheral blood T cells and identified gamma interferon (IFN-γ)-producing CD8+T cells as correlates of protection, which can be induced by prime-boost vaccination with recombinant poxviruses. Invariant natural killer T (Vα14iNKT) cells can also protect against liver stage malaria, when activated, and are abundant in the liver. Since poxviruses have nonspecific immunomodulating effects, which are incompletely understood, we investigated whether recombinant poxviruses affect the protective properties of hepatic Vα14iNKT cells and thus vaccine efficacy. We show that intradermal vaccination with recombinant poxviruses activated Vα14iNKT cells and NK cells in the livers of BALB/c mice while inducing IFN-γ- and tumor necrosis factor alpha (TNF-α)-producing pre-erythrocytic stage antigen-specific CD8+T cells. Greater numbers of hepatic Vα14iNKT cells secreted interleukin-4 than IFN-γ. Vaccinated Vα14iNKT-cell-deficient mice had lower, but still protective levels of hepatic and splenic IFN-γ+and TNF-α+CD8+T cells and better protection rates later after challenge withPlasmodium bergheisporozoites. Therefore, vaccine-activated hepatic Vα14iNKT cells help in generating specific T cells but are not required for protection induced by recombinant poxviruses. Furthermore, double-positive INF-γ+/TNF-α+CD8+T cells were enriched in protected livers, suggesting that cells expressing both of these cytokines may be most relevant for protection.
The M Protein Is Dispensable for Maturation of Streptococcal Cysteine Protease SpeB
Authors: Zimmerlein Björn , Park Hae-Sun , Li Shaoying , Podbielski Andreas , Cleary P. Patrick 
Published: January 2005

ABSTRACTThe streptococcal pyrogenic exotoxin B (SpeB) is an important virulence factor of group A streptococci (GAS) with cysteine protease activity. Maturation of SpeB to a proteolytically active form was suggested to be dependent on cell-wall-anchored M1 protein, the major surface protein of GAS (M. Collin and A. Olsén, Mol. Microbiol.36:1306-1318, 2000). Collin and Olsén showed that mutant GAS strains expressing truncated M protein secrete a conformationally different form of unprocessed SpeB with no proteolytic activity. Alternatively, we hypothesized that a truncated M protein may interfere with processing of this secreted protease, and therefore we tested cysteine protease activity in genetically defined mutant strains that express either no M protein or membrane-anchored M protein with an in-frame deletion of the AB repeat region. Measurements of SpeB activity by cleavage of a substraten-benzoyl-Pro-Phe-Arg-p-nitroanilide hydrochloride showed that the proteolytic activities in culture supernatants of both mutants were similar to those from the wild-type strain. In addition, Western blot analysis of culture supernatants showed that SpeB expression and processing to a mature form was unaffected by either deletion mutation. Therefore, we conclude that M protein is not required for maturation of the streptococcal cysteine protease SpeB.
Solubility and Bioactivity of the
Pseudomonas
Quinolone Signal Are Increased by a
Pseudomonas aeruginosa
-Produced Surfactant
Authors: Calfee M. Worth , Shelton John G. , McCubrey James A. , Pesci Everett C. 
Published: January 2005

ABSTRACT

Pseudomonas aeruginosa
is a gram-negative bacterium that causes serious infections in immunocompromised individuals and cystic fibrosis patients. This opportunistic pathogen controls many of its virulence factors and cellular functions through the activity of three cell-to-cell signals,
N
-(3-oxododecanoyl)-
l
-homoserine lactone,
N
-butyryl-
l
-homoserine lactone, and the
Pseudomonas
quinolone signal (PQS). The activity of these signals is dependent upon their ability to dissolve in and freely diffuse through the aqueous solution in which
P. aeruginosa
happens to reside. Despite this, our data indicated that PQS was relatively insoluble in aqueous solutions, which led us to postulate that
P. aeruginosa
could be producing a PQS-solubilizing factor. In this report, we show that the
P. aeruginosa
-produced biosurfactant rhamnolipid greatly enhances the solubility of PQS in aqueous solutions. The enhanced solubility of PQS led to an increase in PQS bioactivity, as measured by both a gene induction assay and an apoptosis assay. This is the first demonstration of the importance of a bacterial surfactant in the solubilization and bioactivity of a cell-to-cell signal.
A Functional Virulence Complex Composed of Gingipains, Adhesins, and Lipopolysaccharide Shows High Affinity to Host Cells and Matrix Proteins and Escapes Recognition by Host Immune Systems
Authors: Takii Ryosuke , Kadowaki Tomoko , Baba Atsuyo , Tsukuba Takayuki , Yamamoto Kenji 
Published: January 2005

ABSTRACTArg-gingipain (Rgp) and Lys-gingipain (Kgp) arePorphyromonas gingivaliscysteine proteinases implicated as major virulence factors in pathologies of periodontitis. We purified a 660-kDa cell-associated gingipain complex existing as a homodimer of two catalytically active monomers which comprises their catalytic and adhesin domains. Electron microscopy revealed that the complex was composed of a globular particle with a 10-nm external diameter possessing one or two electron-dense hole-like structures. Two-dimensional gel electrophoresis and immunoblot analyses revealed the association of lipopolysaccharide (LPS) with the catalytic domains and a hemagglutinin domain, Hgp44, of Rgp and Kgp in the complex. The complex significantly degraded human type I collagen and elastin and strongly disrupted viability of human gingival fibroblasts and umbilical vein endotherial cells with an efficiency which was higher than that of the monomeric gingipains. The native complex produced only a small amount of nitrogen dioxide, tumor necrosis factor alpha, and interleukin-6 by macrophages, whereas the heat-denatured complex resulted in increased production. Inhibition of the proteolytic activities of the gingipain complex did not up-regulate the cytokine production, indicating that the functional domains in LPS are structurally masked by the complex proteins. These results indicate the importance of the complex in evasion of host defense mechanisms as well as in host tissue breakdown.
Contribution of Three Bile-Associated Loci,bsh,pva, andbtlB, to Gastrointestinal Persistence and Bile Tolerance ofListeria monocytogenes
Authors: Begley Máire , Sleator Roy D. , Gahan Cormac G. M. , Hill Colin 
Published: January 2005

ABSTRACTListeria monocytogenesmust resist the deleterious actions of bile in order to infect and subsequently colonize the human gastrointestinal tract. The molecular mechanisms used by the bacterium to resist bile and the influence of bile on pathogenesis are as yet largely unexplored. This study describes the analysis of three genes—bsh,pva, andbtlB—previously annotated as bile-associated loci in the sequencedL. monocytogenesEGDe genome (lmo2067, lmo0446, and lmo0754, respectively). Analysis of deletion mutants revealed a role for all three genes in resisting the acute toxicity of bile and bile salts, particularly glycoconjugated bile salts at low pH. Mutants were unaffected in the other stress responses examined (acid, salt, and detergents). Bile hydrolysis assays demonstrate thatL. monocytogenespossesses only one bile salt hydrolase gene, namely,bsh. Transcriptional analyses and activity assays revealed that, although it is regulated by both PrfA and σB, the latter appears to play the greater role in modulatingbshexpression. In addition to being incapable of bile hydrolysis, asigBmutant was shown to be exquisitely sensitive to bile salts. Furthermore, increased expression ofsigBwas detected under anaerobic conditions and during murine infection. A gene previously annotated as a possible penicillin V amidase (pva) or bile salt hydrolase was shown to be required for resistance to penicillin V but not penicillin G but did not demonstrate a role in bile hydrolysis. Finally, animal (murine) studies revealed an important role for bothbshandbtlBin the intestinal persistence ofL. monocytogenes.
TheSalmonella entericaSerovar Typhimurium-Encoded Type III Secretion Systems Can TranslocateChlamydia trachomatisProteins into the Cytosol of Host Cells
Authors: Ho Theresa D. , Starnbach Michael N. 
Published: January 2005

ABSTRACTChlamydia trachomatisis an obligate, intracellular pathogen that is a major cause of preventable blindness and infertility worldwide. Although the published genome sequence suggests thatC. trachomatisencodes a type III secretion system, the lack of genetic tools for studyingChlamydiahas hindered the examination of this potentially important class of virulence genes. We have developed a technique to identifyChlamydiaproteins that can be translocated into the host cell cytoplasm by a type III secretion system. We have selected severalChlamydiaproteins and tagged them with a multiple peptide motif element called F8M4. Epitopes contained in the F8M4 tag allow us to use tools corresponding to different arms of the adaptive immune system to detect the expression and translocation of these proteins bySalmonella entericaserovar Typhimurium. In particular, CD8+-T-cell reactivity can be used to detect the translocation of F8M4-tagged proteins into the cytoplasm of host cells. We have found that CD8+-T-cell activity assays are sensitive enough to detect translocation of even a small amount of F8M4-tagged protein. We have used CD8+-T-cell activity to show that CopN, aChlamydiaprotein previously shown to be translocated byYersiniatype III secretion, can be translocated by theSalmonellapathogenicity island 1 (SPI-1) type III secretion system. Additionally, we demonstrate that CopD and Pkn5, twoChlamydiaproteins hypothesized to be substrates of a type III secretion system, are translocated via the SPI-2 type III secretion system of serovar Typhimurium. The epitope tag system described here can be used more generally to examine the expression and subcellular compartmentalization of bacterial proteins deployed during the interaction of pathogens with mammalian cells.
ProbioticLactobacillusspp. DiminishHelicobacter hepaticus-Induced Inflammatory Bowel Disease in Interleukin-10-Deficient Mice
Authors: Peña Jeremy A. , Rogers Arlin B. , Ge Zhongming , Ng Vivian , Li Sandra Y. , Fox James G. , Versalovic James 
Published: January 2005

ABSTRACTClinical and experimental evidence has demonstrated the potential role of probiotics in the prevention or treatment of inflammatory bowel disease. Probiotic clones with direct immunomodulatory activity may have anti-inflammatory effects in the intestine. We investigated the roles of tumor necrosis factor alpha (TNF-α)-inhibitoryLactobacillusclones with a pathogen-induced murine colitis model. Murine-derived probiotic lactobacilli were selected in vitro for their ability to inhibit TNF-α secretion byHelicobacter hepaticus-stimulated macrophages. Interleukin-10 (IL-10)-deficient mice were treated with probioticLactobacillus reuteriin combination withLactobacillus paracaseiand then challenged withH. hepaticus. Ten weeks postinoculation, the severity of typhlocolitis was assessed by histologic examination of the cecocolic region. Intestinal proinflammatory cytokine responses were evaluated by real-time quantitative reverse transcriptase PCR and immunoassays, and the quantities of intestinalH. hepaticuswere evaluated by real-time PCR. Intestinal colonization by TNF-α-inhibitory lactobacilli reduced intestinal inflammation inH. hepaticus-challenged IL-10-deficient mice despite similar quantities ofH. hepaticusin cocolonized animals. Proinflammatory colonic cytokine (TNF-α and IL-12) levels were lowered inLactobacillus-treated animals. In thisH. hepaticus-challenged IL-10-deficient murine colitis model, lactobacilli demonstrated probiotic effects by direct modulation of mucosal inflammatory responses.
Cytokine Profiling of Macrophages Exposed toPorphyromonas gingivalis, Its Lipopolysaccharide, or Its FimA Protein
Authors: Zhou Qingde , Desta Tesfahun , Fenton Matthew , Graves Dana T. , Amar Salomon 
Published: January 2005

ABSTRACTTo characterize the roles ofPorphyromonas gingivalisand its components in the disease processes, we investigated the cytokine profile induced by liveP. gingivalis, its lipopolysaccharides (LPS), and its major fimbrial protein, fimbrillin (FimA). Using cytokine antibody arrays, we found thatP. gingivalisLPS and FimA induced a similar profile of cytokine expression when exposed to mouse peritoneal macrophages but that this profile differed significantly in response to liveP. gingivalis. In vitro, mouse peritoneal macrophages were stimulated to produce interleukin-6 (IL-6), granulocyte colony-stimulating factor, and lymphotactin by liveP. gingivalis, but not byP. gingivalisLPS or FimA, while RANTES, gamma interferon, IL-17, vascular cell adhesion molecule 1 (VCAM-1), and vascular endothelial growth factor were induced byP. gingivalisLPS or FimA, but not by liveP. gingivalis. In vivo, IL-6 mRNA was strongly induced only by liveP. gingivaliswhile monocyte chemoattractant protein 1 mRNA was strongly induced only byP. gingivalisLPS and FimA in mouse calvarial scalp, further confirming the differences of cytokine profile induced in vitro. Cytokine antibody arrays using toll-like receptor 2 (TLR2)- and TLR4-deficient macrophages revealed that most of the cytokines induced byP. gingivalisLPS or FimA signal through TLR2, while most of cytokines induced by liveP. gingivalissignal through both TLR2 and TLR4. Interestingly, the activation of TLR2 by liveP. gingivalisinhibited the release of RANTES, VCAM-1, and IL-1α from mouse peritoneal macrophages. A tumor necrosis factor alpha enzyme-linked immunosorbent assay further confirmed thatP. gingivalisLPS and FimA activate mouse peritoneal macrophages via TLR2. These results indicate that host immune cells sense liveP. gingivalisand its components differently, which translates into the expression of different inflammatory cytokine profiles.
The IrgA Homologue Adhesin Iha Is an
Escherichia coli
Virulence Factor in Murine Urinary Tract Infection
Authors: Johnson James R. , Jelacic Srdjan , Schoening Laura M. , Clabots Connie , Shaikh Nurmohammad , Mobley Harry L. T. , Tarr Phillip I. 
Published: January 2005

ABSTRACT

The role of the
Escherichia coli
iron-regulated gene homologue adhesin (Iha) in the pathogenesis of urinary tract infections (UTIs) is unknown. We performed a series of complementary analyses to confirm or refute the hypothesis that Iha is a virulence factor in uropathogenic
E. coli
. Fecal
E. coli
isolates exhibited significantly lower prevalences of
iha
(range, 14 to 22%) than did clinical isolates from cases of pediatric cystitis or pyelonephritis, adult pyelonephritis or urosepsis, or bacteremia (range, 38 to 74%). Recombinant Iha from
E. coli
pyelonephritis isolate CFT073 conferred upon nonadherent
E. coli
ORN172 the ability to adhere to cultured T-24 human uroepithelial cells. In a well-established mouse model of ascending UTI, CFT073 and its derivative UPEC76 (a
pap
[P fimbriae] mutant version of strain CFT073) each significantly outcompeted their respective
iha
deletion mutants in CBA/J mice 48 h after bladder challenge (
P
< 0.03 for urine, both kidneys, and bladders of both constructs, except for bladders of mice challenged with UPEC76 and its deletion mutant, where
P
= 0.11). These data suggest that Iha
CFT073
is a virulence factor and might be a target for anti-UTI interventions.
PppA, a Surface-Exposed Protein ofStreptococcus pneumoniae, Elicits Cross-Reactive Antibodies That Reduce Colonization in a Murine Intranasal Immunization and Challenge Model
Authors: Green Bruce A. , Zhang Ying , Masi Amy W. , Barniak Vicki , Wetherell Michael , Smith Robert P. , Reddy Molakala S. , Zhu Duzhang 
Published: January 2005

ABSTRACTThe multivalent pneumococcal conjugate vaccine is effective against both systemic disease and otitis media caused by serotypes contained in the vaccine. However, serotypes not covered by the present conjugate vaccine may still cause pneumococcal disease. To address these serotypes, and the remaining otitis media due toStreptococcus pneumoniae, efforts have been devoted to identifying protective protein antigens. Immunity to conserved surface proteins important for adhesion, nutrient acquisition, or other functions could result in a reduction of colonization and a lower disease potential. We have been searching for conserved surface-exposed proteins fromS. pneumoniaethat may be involved in pathogenesis to test as vaccine candidates. Here, an ∼20-kDa protein that has significant homology to a nonheme iron-containing ferritin protein fromListeria innocuaand other bactoferritins was identified as pneumococcal protective protein A (PppA). We expressed and purified recombinant PppA (rPppA) and evaluated its potential as a vaccine candidate. The antibodies elicited by purified rPppA were cross-reactive with PppA from multiple strains ofS. pneumoniaeand were directed against surface-exposed epitopes. Intranasal immunization of BALB/c mice with PppA protein and either a synthetic monophosphoryl lipid A analog, RC529AF, or a cholera toxin mutant, CT-E29H, used as an adjuvant reduced nasopharyngeal colonization in mice following intranasal challenge with a heterologous pneumococcal strain. PppA-specific systemic and local immunoglobulin G (IgG) and IgA antibody responses were induced. The antisera reacted with whole cells of a heterologousS. pneumoniaetype 3 strain. These observations indicate that PppA may be a promising candidate for inclusion in a vaccine against pneumococcal otitis media.
Synthetic Studies Toward Chiral Aromatic Triynes as Key Substrates for the Asymmetric Synthesis of Helicene-Like Molecules
Authors: Alexandrová Zuzana , Stará Irena G. , Sehnal Petr , Teplý Filip , Starý Ivo , Šaman David , Fiedler Pavel 
Published: January 2005

We have developed the synthesis of model nonracemic aromatic triynes (-)-(S)-1-4 containing the 1-{[2-(but-3-yn-1-yl)-1-naphthyl]ethynyl}-2-{[((S)-1-methylprop-2-yn-1-yl)oxy]- methyl}naphthalene unit. The common 1,2-di(2-substituted-1-naphthyl)acetylene part was constructed via Sonogashira coupling of appropriate 1-iodonaphthalenes with 1-ethynylnaphthalenes both bearing tethered acetylene units in positions 2. The chirality of triynes (-)-(S)-1-4 was introduced by incorporating commercially available (-)-(S)-but-3-yn-2-ol (10) into tethered acetylene units. The nonracemic triynes are intended to be used as substrates in stereoselective [2+2+2] triyne cycloisomerization catalyzed by transition metal complexes.