bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cysteine Protease Secreted byParagonimus westermaniAttenuates Effector Functions of Human Eosinophils Stimulated with Immunoglobulin G
Authors: Shin Myeong Heon , Kita Hirohito , Park Hae Young , Seoh Ju Young 
Published: July 2002

ABSTRACTAn immunoglobulin G (IgG)-coated surface, such as that found on helminth parasites, is one of the most effective physiologic stimuli for eosinophil activation. The cysteine proteases secreted by tissue-invasive helminth larvae play an important role in evasion of the immune response by degrading the host immunoglobulins. In this study, we investigated whether cysteine proteases in the excretory-secretory product (ESP) produced byParagonimus westermaninewly excysted metacercariae (PwNEM), which cause pulmonary or extrapulmonary paragonimiasis in human beings, could modify effector functions of human eosinophils stimulated with IgG. We coated 96-well plates with human IgG in the absence or presence of the ESP produced by PwNEM. When eosinophils were incubated in the wells coated with IgG in the presence of the ESP, eosinophil degranulation and superoxide production were significantly reduced compared with results for cells incubated in wells coated with IgG alone. This inhibitory effect of the ESP on IgG-induced superoxide production was dose dependent and was significantly abolished by pretreatment of the ESP with heat. These findings suggest that the cysteine proteases secreted by PwNEM attenuate both activation and degranulation of eosinophils stimulated with IgG. Thus, the cysteine proteases produced by tissue-invasive helminth larvae play crucial roles in evasion of IgG-dependent eosinophil helminthotoxicity and in reduction of eosinophil-associated tissue inflammation during the migratory period.
Two Epitopes Shared by
Taenia crassiceps
and
Taenia solium
Confer Protection against Murine
T. crassiceps
Cysticercosis along with a Prominent T1 Response
Authors: Toledo Andrea , Fragoso Gladis , Rosas Gabriela , Hernández Marisela , Gevorkian Goar , López-Casillas Fernando , Hernández Beatriz , Acero Gonzalo , Huerta Mirna , Larralde Carlos , Sciutto Edda 
Published: July 2002

ABSTRACT

Taenia crassiceps
recombinant antigens KETc1 and KETc12 have been shown to induce high level of protection against experimental murine
T. crassiceps
cysticercosis, an experimental model successfully used to test candidate antigens for use in vaccination against porcine
Taenia solium
cysticercosis. Based on the deduced amino acid sequence, KETc1 and KETc12 were chemically synthesized in linear form. Immunization with KETc1 induced 66.7 to 100% protection against murine cysticercosis, and immunization with KETc12 induced 52.7 to 88.1% protection. The elicited immune response indicated that both peptides contain at least one B-cell epitope (as demonstrated by their ability to induce specific antibodies) and one T-cell epitope that strongly stimulated the proliferation of T cells primed with either the free peptide or total cysticercal
T. crassiceps
antigens. The high percentage of spleen cells expressing inflammatory cytokines points to the likelihood of a T1 response being involved in protection. The protective capacity of the peptides and their presence in all developmental stages of
T. solium
point to these two epitopes as strong candidates for inclusion in a polyepitopic synthetic vaccine against
T. solium
pig cysticercosis.
Spa33, a Cell Surface-Associated Subunit of the Mxi-Spa Type III Secretory Pathway of
Shigella flexneri
, Regulates Ipa Protein Traffic
Authors: Schuch Raymond , Maurelli Anthony T. 
Published: July 2002

ABSTRACT

The Mxi-Spa type III secretion system of
Shigella flexneri
directs the host cell contact-induced secretion of a set of invasins, referred to as Ipas. In this study, we examined the role of Spa33 in Ipa secretion. A
spa33
-null mutant was both noninvasive and unable to translocate the Ipas from inner membrane to outer membrane (OM) positions of the Mxi-Spa transmembrane channel. Spa33 was found to be a Mxi-Spa substrate that is translocated to the bacterial cell surface upon the induction of Ipa secretion. This mobility may serve to drive Ipa translocation within Mxi-Spa toward OM positions. Consistent with a second distinct role in regulating Ipa traffic, the overexpression of Spa33 also blocked Ipa secretion and resulted in Ipa accumulation at the OM. Co-overexpression of Spa33 and another OM-associated element, Spa32, did not disrupt Ipa secretion, suggesting an interaction between the two proteins and an effect on the mechanism which serves to regulate Ipa release from the OM. These findings indicate that Spa33 is a mobile element within Mxi-Spa, which is required to control Ipa translocation into and out of OM positions of the secretory structure.
Induction of Cell-Associated Chemokines after Endotoxin Administration to Healthy Humans
Authors: Olszyna Dariusz P. , De Jonge Evert , Dekkers Pascale E. P. , van Deventer Sander J. H. , van der Poll Tom 
Published: July 2002

ABSTRACTErythrocytes express the Duffy antigen receptor for chemokines. Endotoxin injection into humans induced high levels of interleukin-8 (IL-8), growth-related oncogene α, and monocyte chemoattractant protein 1 in circulating erythrocytes. IL-8 was also recovered from mononuclear and polymorphonuclear cells. Cell-associated chemokines may more accurately reflect their production than plasma concentrations.
Protection against Cutaneous Leishmaniasis Induced by Recombinant Antigens in Murine and Nonhuman Primate Models of the Human Disease
Authors: Campos-Neto Antonio , Porrozzi Renato , Greeson Kay , Coler Rhea N. , Webb John R. , Seiky Yasir A. W. , Reed Steven G. , Grimaldi Gabriel 
Published: July 2002

ABSTRACTLeishmaniasis affects approximately 2 million people each year throughout the world. This high incidence is due in part to the lack of an efficacious vaccine. We present evidence that the recombinant leishmanial antigens LmSTI1 and TSA, which we identified and characterized previously, induce excellent protection in both murine and nonhuman primate (rhesus monkey) models of human cutaneous leishmaniasis. The remarkable protection induced by LmSTI1 and TSA in an animal model that is evolutionarily close to humans qualifies this antigen combination as a promising candidate subunit vaccine against human leishmaniasis.
Decreased Apoptosis in the Ileum and Ileal Peyer's Patches: a Feature after Infection with Rabbit Enteropathogenic
Escherichia coli
O103
Authors: Heczko Ursula , Carthy Chris M. , O'Brien Bronwyn A. , Finlay B. Brett 
Published: July 2002

ABSTRACT

Significant changes occur in intestinal epithelial cells after infection with enteropathogenic
Escherichia coli
(EPEC). However, it is unclear whether this pathogen alters rates of apoptosis. By using a naturally occurring weaned rabbit infection model, we determined physiological levels of apoptosis in rabbit ileum and ileal Peyer's patches (PP) and compared them to those found after infection with adherent rabbit EPEC (REPEC O103). Various REPEC O103 strains were first tested in vitro for characteristic virulence features. Rabbits were then inoculated with the REPEC O103 strains that infected cultured cells the most efficiently. After experimental infection, intestinal samples were examined by light and electron microscopy. Simultaneously, ileal apoptosis was assessed by using terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and caspase 3 assays and by apoptotic cell counts based on morphology (hematoxylin-and-eosin staining). The highest physiological apoptotic indices were measured in PP germinal centers (median = 14.7%), followed by PP domed villi (8.1%), tips of absorptive villi (3.8%), and ileal crypt regions (0.5%). Severe infection with REPEC O103 resulted in a significant decrease in apoptosis in PP germinal centers (determined by TUNEL assay;
P
= 0.01), in the tips of ileal absorptive villi (determined by H&E staining;
P
= 0.04), and in whole ileal cell lysates (determined by caspase 3 assay;
P
= 0.001). We concluded that REPEC O103 does not promote apoptosis. Furthermore, we cannot rule out the possibility that REPEC O103, in fact, decreases apoptotic levels in the rabbit ileum.
Intranasal Immunization with Killed Unencapsulated Whole Cells Prevents Colonization and Invasive Disease by Capsulated Pneumococci
Authors: Malley Richard , Lipsitch Marc , Stack Anne , Saladino Richard , Fleisher Gary , Pelton Steven , Thompson Claudette , Briles David , Anderson Porter 
Published: July 2002

ABSTRACT
A whole-cell killed unencapsulated pneumococcal vaccine given by the intranasal route with cholera toxin as an adjuvant was tested in two animal models. This vaccination was highly effective in preventing nasopharyngeal colonization with an encapsulated serotype 6B strain in mice and also conferred protection against illness and death in rats inoculated intrathoracically with a highly encapsulated serotype 3 strain. When the serotype 3 challenge strain was incubated in the sera of immunized rats, it was no longer virulent in an infant-rat sepsis model, indicating that the intranasal immunization elicited protective systemic antibodies. These studies suggest that killed whole-cell unencapsulated pneumococci given intranasally with an adjuvant may provide multitypic protection against capsulated pneumococci.
Neisseria meningitidisLipopolysaccharide Modulates the Specific Humoral Immune Response to Neisserial Porins but Has No Effect on Porin-Induced Upregulation of Costimulatory Ligand B7-2
Authors: Bhasin Navneet , Ho Yu , Wetzler Lee M. 
Published: July 2002

ABSTRACTThe role of lipopolysaccharide (LPS) in the specific humoral response to meningococcal porins was investigated by measuring anti-PorA or -PorB antibody levels in mice immunized with wild-type meningococcal strain H44/76 or with its recently described LPS-negative mutant. Two murine strains were used for these immunizations: C3H/HeJ, which is LPS hyporesponsive, or C3H/HeOuJ, which is LPS responsive. A high level of anti-PorB immunoglobulin G (IgG) response was induced in both strains of mice immunized with either organism. The response induced by the wild-type strain was greater in C3H/HeOuJ mice than in C3H/HeJ mice, while the response induced by the LPS-negative mutant was similar in the two murine strains. Additionally, the anti-PorB response was similar in C3H/HeJ mice immunized with either bacterial strain. In general, the anti-PorA IgG response was lower than the anti-PorB response. These findings indicate that the presence of LPS is not essential for the induction of an antineisserial porin humoral response but can augment such a response. To determine whether LPS has any effect on the B-cell-stimulatory effect of neisserial porins (essential for the adjuvant activity of neisserial porins), B cells from both murine strains were incubated with outer membrane complexes (OMCs) prepared from strain H44/76 and its LPS-negative mutant. OMCs from either meningococcal strain were able to increase the surface expression of the costimulatory ligand B7-2 on B cells from either murine strain. Consistent with previously reported findings, LPS does not significantly affect the ability of neisserial porins to induce the costimulatory ligand B7-2.
Cholera Toxin B Subunit as a Carrier Molecule Promotes Antigen Presentation and Increases CD40 and CD86 Expression on Antigen-Presenting Cells
Authors: George-Chandy Annie , Eriksson Kristina , Lebens Michael , Nordström Inger , Schön Emma , Holmgren Jan 
Published: July 2002

ABSTRACTCholera toxin B subunit (CTB) is an efficient mucosal carrier molecule for the generation of mucosal antibody responses and/or induction of systemic T-cell tolerance to linked antigens. CTB binds with high affinity to GM1 ganglioside cell surface receptors. In this study, we evaluated how conjugation of a peptide or protein antigen to CTB by chemical coupling or genetic fusion influences the T-cell-activating capacity of different antigen-presenting cell (APC) subsets. Using an in vitro system in which antigen-pulsed APCs were incubated with antigen-specific, T-cell receptor-transgenic T cells, we found that the dose of antigen required for T-cell activation could be decreased >10,000-fold using CTB-conjugated compared to free antigen. In contrast, no beneficial effects were observed when CTB was simply admixed with antigen. CTB conjugation enhanced the antigen-presenting capacity not only of dendritic cells and B cells but also of macrophages, which expressed low levels of cell surface major histocompatibility complex (MHC) class II and were normally poor activators of naive T cells. Enhanced antigen-presenting activity by CTB-linked antigen resulted in both increased T-cell proliferation and increased interleukin-12 and gamma interferon secretion and was associated with up-regulation of CD40 and CD86 on the APC surface. These results imply that conjugation to CTB dramatically lowers the threshold concentration of antigen required for immune cell activation and also permits low-MHC II-expressing APCs to prime for a specific immune response.
Sensitivities of Human Monocytes and Epithelial Cells to Pneumolysin Are Different
Authors: Hirst Robert A. , Yesilkaya Hasan , Clitheroe Edwin , Rutman Andrew , Dufty Nichola , Mitchell Timothy J. , O’Callaghan Christopher , Andrew Peter W. 
Published: July 2002

ABSTRACTTheStreptococcus pneumoniaepore-forming toxin, pneumolysin, is an important virulence factor in pneumococcal pneumonia. The effect of pneumolysin on human lung epithelial and monocyte cell viability was compared. Pneumolysin caused a dose-dependent loss of viability of human lung epithelial (A549 and L132) and monocyte (U937 and THP-1) cell lines. Analysis of the dose-response curves revealed similar log 50% inhibitory concentration (pIC50) values for A549, L132, and THP-1 of 0.12± 0.1, 0.02± 0.04, and 0.12± 0.13 hemolytic units (HU), respectively, but U937 cells showed a significantly greater pIC50of 0.42± 0.12 HU. Differentiation of A549 and L132 with phorbol ester or THP-1 with gamma interferon had no effect on their sensitivity to pneumolysin. However, a significant decrease in the potency of pneumolysin against U937 cells followed gamma interferon treatment. The Hill slopes of the inhibition curves were greater than unity, indicating that pneumolysin may act with positive cooperativity. Analysis of pneumolysin-treated THP-1 cells by electron microscopy revealed membrane lesions of between 100 and 200 nm in diameter.
Replication of
Neisseria meningitidis
within Epithelial Cells Requires TonB-Dependent Acquisition of Host Cell Iron
Authors: Larson Jason A. , Higashi Dustin L. , Stojiljkovic Igor , So Magdalene 
Published: July 2002

ABSTRACT

Neisseria meningitidis
(meningococcus [MC]) is able to enter and replicate within epithelial cells. Iron, an essential nutrient for nearly all organisms, is an important determinant in the ability of MC to cause disease; however, its role in MC intracellular replication has not been investigated. We analyzed the growth of MC within the A431 human epithelial cell line and the dependence of this growth on iron uptake. We present evidence here that chelation of iron from infected tissue culture cells with Desferal strongly inhibited intracellular replication of wild-type (wt) MC. We also provide genetic evidence that iron must be acquired by MC from the host cell in order for it to replicate. An
hmbR
mutant that is unable to use hemoglobin iron and could not grow in tissue culture media without iron supplementation replicated more rapidly within epithelial cells than its wt parent strain. An
fbpA
mutant that is unable to utilize human transferrin iron or lactoferrin iron replicated normally within cells. In contrast, a
tonB
mutant could not replicate intracellularly unless infected cultures were supplemented with ferric nitrate. Taken together, these findings strongly suggest that MC intracellular replication requires TonB-dependent uptake of a novel host cell iron source.
Naturally Exposed Populations Differ in Their T1 and T2 Responses to the Circumsporozoite Protein ofPlasmodium falciparum
Authors: Reece W. H. H. , Plebanski M. , Akinwunmi P. , Gothard P. , Flanagan K. L. , Lee E. A. M. , Cortina-Borja M. , Hill A. V. S. , Pinder M. 
Published: July 2002

ABSTRACTT-cell responses directed against the circumsporozoite protein (CS) ofPlasmodium falciparumcan mediate protection against malaria. We determined the frequency of T cells reactive to different regions of the CS in the blood of donors naturally exposed toP. falciparumby examining T1 (gamma interferon [IFN-γ] ELISPOT assay), T2 (interleukin 4 [IL-4] ELISPOT assay), and proliferative T-cell responses. The proliferative responses were weak, which confirmed previous observations. The responses to the CS in the IL-4 and IFN-γ ELISPOT assays were also weak (<40 responding cells per 106cells), much weaker than the response to the purified protein derivative ofMycobacterium tuberculosisin the same donors. Moreover, a response in one assay could not be used to predict a response in either of the other assays, suggesting that although these assays may measure different responding cells, all of the responses are weakly induced by natural exposure. Interestingly, the two different study populations used had significantly different T1 and T2 biases in their responses in the C terminus of the protein, suggesting that the extent ofP. falciparumexposure can affect regulation of the immune system.
Receptor-Based Antidote for Diphtheria
Authors: Cha Jeong-Heon , Brooke Joanna S. , Chang Mee Young , Eidels Leon 
Published: July 2002

ABSTRACT
Although equine diphtheria antitoxin may be an effective therapy for human diphtheria, its use often induces serum sickness. We describe here a strategy for developing an alternative treatment based on the human diphtheria toxin (DT) receptor/heparin-binding epidermal growth factor-like growth factor (HB-EGF) precursor. Recombinant mature human HB-EGF acts as a soluble receptor analog, binding radioiodinated DT and preventing its binding to the cellular DT receptor/HB-EGF precursor. However, the possibility existed that radioiodinated DT-HB-EGF complexes associate with cells due to the binding of the heparin-binding domain of recombinant HB-EGF to cell surface heparan sulfate proteoglycans. This possibility was confirmed by performing DT binding studies in the presence of heparin. A recombinant truncated HB-EGF (residues 106 to 149), which lacks most of the heparin-binding domain, showed an essentially heparin-independent binding of radioiodinated DT to cells. Furthermore, it was a more effective inhibitor of DT binding than was recombinant mature HB-EGF. Since mature HB-EGF is a known ligand for the EGF receptor and is thus highly mitogenic (tumorigenic), we then changed amino acid residues in the EGF-like domain of the recombinant truncated HB-EGF and demonstrated that this DT receptor analog (I117A/L148A) displayed a low mitogenic effect. The truncated (I117A/L148A) HB-EGF protein retained high DT binding affinity, as confirmed by using surface plasmon resonance. Our results suggest that the truncated (I117A/L148A) HB-EGF protein could be an effective, safe antidote for human diphtheria.
Immunoglobulin G Monoclonal Antibodies toCryptococcus neoformansProtect Mice Deficient in Complement Component C3
Authors: Shapiro Scott , Beenhouwer David O. , Feldmesser Marta , Taborda Carlos , Carroll Michael C. , Casadevall Arturo , Scharff Matthew D. 
Published: July 2002

ABSTRACTPassive administration of monoclonal antibodies (MAbs) to the capsular polysaccharide ofCryptococcus neoformanscan alter the course of infection in mice. In a murine model of cryptococcal infection, immunoglobulin G1 (IgG1), IgG2a, and IgG2b switch variants of the anti-capsular 3E5 MAb prolong the survival of lethally infected mice, whereas the 3E5 IgG3 MAb does not protect and in some cases enhances infection, shortening the life spans of infected mice. We examined the role of complement component C3 in Ab-mediated protection by determining the efficacy of the four mouse IgG subclasses againstC. neoformansin mice genetically deficient in factor C3 as well as mice acutely depleted of C3. Similar to other complement-deficient animal models, C3−/−mice and mice depleted of C3 by cobra venom factor were more susceptible toC. neoformansinfection than control mice, providing further evidence that complement is important in the host defense against the fungus. In the absence of C3, all IgG isotypes prolonged the lives of mice infected withC. neoformans, indicating that protection by IgG does not require the complement pathways. Furthermore, we observed protection with IgG3 in the complement-deficient mice, suggesting that complement is involved in the lack of protection observed with IgG3 in other mouse models.
Lipopolysaccharide Down Regulates Both Scavenger Receptor B1 and ATP Binding Cassette Transporter A1 in RAW Cells
Authors: Baranova Irina , Vishnyakova Tatyana , Bocharov Alexander , Chen Zhigang , Remaley Alan T. , Stonik John , Eggerman Thomas L. , Patterson Amy P. 
Published: July 2002

ABSTRACTLipopolysaccharide (LPS) has recently been shown to facilitate macrophage foam cell formation and has been suggested to be a proatherogenic factor. The mechanism of LPS induced cholesterol accumulation, however, is unclear. In this report, using the macrophage-like RAW 264.7 cell line, we provide experimental evidence that LPS's proatherogenic effects may at least in part reflect altered cholesterol metabolism. Data presented demonstrate that in a dose-dependent manner, LPS is able to down regulate the mRNA expression of the two primary high-density lipoprotein (HDL) receptors, scavenger receptor B1 (SR-B1) and ATP binding cassette A1 (ABCA1), with a 50% inhibitory concentration of less than 0.2 ng/ml, as well as to decrease SR-B1 protein expression by 80%. We also found that LPS treatment resulted in a significant decrease (to 20% of the control level) of the specific125I-HDL binding as well as in 50% inhibition of the HDL-mediated cholesterol efflux compared to untreated cells. In addition, we compared the potencies of various modified LPS preparations and demonstrated that the phosphorylated lipid A portion of LPS, which is highly conserved among gram-negative microorganisms, includingChlamydia, is primarily responsible for the effects of LPS on SR-B1 and ABCA1 expression. Inhibitors of NF-κB activation were observed to efficiently block the suppressive effect of LPS on SR-B1 and ABCA1, suggesting a mechanism involving NF-κB. These data indicate that the LPS effects on cholesterol metabolism may contribute to the proatherogenic properties of LPS.