bluuebunny/crossref_metadata_2025_split huggingface dataset:
Occurrence of Severe Destructive Lyme Arthritis in Hamsters Vaccinated with Outer Surface Protein A and Challenged withBorrelia burgdorferi
Authors: Croke Cindy L. , Munson Erik L. , Lovrich Steven D. , Christopherson John A. , Remington Monica C. , England Douglas M. , Callister Steven M. , Schell Ronald F. 
Published: July 2002

ABSTRACTArthritis is a frequent and major complication of infection withBorrelia burgdorferisensu stricto. The antigens responsible for the induction of arthritis are unknown. Here we provide direct evidence that a major surface protein, outer surface protein A (OspA), can induce arthritis. Hamsters were vaccinated with 30, 60, or 120 μg of recombinant OspA (rOspA) in aluminum hydroxide and challenged withB. burgdorferisensu stricto isolate 297 or C-1-11. Swelling of the hind paws was detected in 100, 100, and 50% of hamsters vaccinated with 30, 60, or 120 μg of rOspA, respectively. In addition, arthritis developed in 57% of hamsters vaccinated with a canine rOspA vaccine after infection withB. burgdorferisensu stricto. When the canine rOspA vaccine was combined with aluminum hydroxide, all vaccinated hamsters developed arthritis after challenge withB. burgdorferisensu stricto. Histopathologic examination confirmed the development of severe destructive arthritis in rOspA-vaccinated hamsters challenged withB. burgdorferisensu stricto. These findings suggest that rOspA vaccines should be modified to eliminate epitopes of OspA responsible for the induction of arthritis. Our results are important because an rOspA vaccine in aluminum hydroxide was approved by the Food and Drug Administration for use in humans.
Bacterial Phosphorylcholine Decreases Susceptibility to the Antimicrobial Peptide LL-37/hCAP18 Expressed in the Upper Respiratory Tract
Authors: Lysenko Elena S. , Gould Jane , Bals Robert , Wilson James M. , Weiser Jeffrey N. 
Published: July 2002

ABSTRACT

A number of pathogens of the upper respiratory tract express an unusual prokaryotic structure, phosphorylcholine (ChoP), on their cell surface. We tested the hypothesis that ChoP, also found on host membrane lipids in the form of phosphatidylcholine, acts so as to decrease killing by antimicrobial peptides that target differences between bacterial and host membranes. In
Haemophilus influenzae
, ChoP is a phase-variable structure on the oligosaccharide portion of the lipopolysaccharide (LPS). There was a bactericidal effect of the peptide LL-37/hCAP18 on a nontypeable
H. influenzae
strain, with an increasing selection for the ChoP
+
phase as the concentration of the peptide was raised from 0 to 10 μg/ml. Moreover, constitutive ChoP-expressing mutants of unrelated strains showed up to 1,000-fold-greater survival compared to mutants without ChoP. The effect of ChoP on resistance to killing by LL-37/hCAP18 was dependent on the salt concentration and was observed only when bacteria were grown in the presence of environmental choline, a requirement for the expression of ChoP on the LPS. Further studies established that there is transcription of the LL-37/hCAP18 gene on the epithelial surface of the human nasopharynx in situ and inducible transcription in epithelial cells derived from the upper airway. The presence of highly variable amounts of LL-37/hCAP18 in normal nasal secretions (<1.2 to >80 μg/ml) was demonstrated with an antibody against this peptide. It was concluded that ChoP alters the bacterial cell surface so as mimic host membrane lipids and decrease killing by LL-37/hCAP18, an antimicrobial peptide that may be expressed on the mucosal surface of the nasopharynx in bactericidal concentrations.
Dual Role for Transforming Growth Factor β-Dependent Signaling in
Trypanosoma cruzi
Infection of Mammalian Cells
Authors: Hall Belinda S. , Pereira Miercio A. 
Published: July 2002

ABSTRACT

Expression of functional transforming growth factor β (TGF-β) receptors (TβR) is required for the invasion of mammalian cells by the protozoan parasite
Trypanosoma cruzi
. However, the precise role of this host cell signaling complex in
T. cruzi
infection is unknown. To investigate the role of the TGF-β signaling pathway, infection levels were studied in the mink lung epithelial cell lines JD1, JM2, and JM3. These cells express inducible mutant TβR1 proteins that cannot induce growth arrest in response to TGF-β but still transmit the signal for TGF-β-dependent gene expression. In the absence of mutant receptor expression, trypomastigotes invaded the cells at a low level. Induction of the mutant receptors caused an increase in infection in all three cell lines, showing that the requirement for TGF-β signaling at invasion can be divorced from TGF-β-induced growth arrest. TGF-β pretreatment of mink lung cells expressing wild-type TβR1 caused a marked enhancement of infection, but no enhancement was seen in JD1, JM2, and JM3 cells, showing that the ability of TGF-β to stimulate infection is associated with growth arrest. Likewise, expression of SMAD7 or SMAD2SA, inhibitors of TGF-β signaling, did not block infection by
T. cruzi
but did block the enhancement of infection by TGF-β. Taken together, these results show that there is a dual role for TGF-β signaling in
T. cruzi
infection. The initial invasion of the host cell is independent of both TGF-β-dependent gene expression and growth arrest, but TGF-β stimulation of infection requires a fully functional TGF-β signaling pathway.
Upregulation of Monocyte Urokinase Plasminogen Activator Receptor during Human Endotoxemia
Authors: Dekkers Pascale E. P. , ten Hove Tessa , te Velde Anje A. , van Deventer Sander J. H. , van der Poll Tom 
Published: July 2002

ABSTRACTThe receptor for urokinase-type plasminogen activator (uPAR) (CD87) plays an important role in leukocyte adhesion and migration. To assess the effect of endotoxin on cellular uPAR, uPAR expression was determined on leukocytes by fluorescence-activated cell sorter analysis in seven healthy subjects following intravenous injection of endotoxin (lot G; 4 ng/kg). Endotoxin induced a transient increase in uPAR expression on monocytes, reaching a 92% ± 46% increase over baseline expression after 6 h (P< 0.05). Endotoxin did not influence uPAR expression on granulocytes, while uPAR remained undetectable on lymphocytes. Endotoxin also increased soluble uPAR levels in plasma (P< 0.05). Stimulation of human whole blood with endotoxin or gram-positive stimuli in vitro also resulted in an upregulation of monocyte uPAR expression. Although tumor necrosis factor alpha (TNF) upregulated monocyte uPAR expression, anti-TNF did not influence the endotoxin-induced increase in monocyte uPAR expression. These data suggest that infectious stimuli may influence monocyte function in vivo by enhancing the expression of uPAR.
Motility Is Required To Initiate Host Cell Invasion by
Yersinia enterocolitica
Authors: Young Glenn M. , Badger Julie L. , Miller Virginia L. 
Published: July 2002

ABSTRACT

Invasin-mediated invasion of host cells by the pathogen
Yersinia enterocolitica
was shown to be affected by flagellar-dependent motility. Motility appears to be required to ensure the bacterium migrates to and contacts the host cell. Nonmotile strains of
Y. enterocolitica
were less invasive than motile strains, but the reduction in invasion could be overcome by artificially bringing the bacteria into host cell contact by centrifugation. Mutations in known regulatory genes of the flagellar regulon,
flhDC
and
fliA
, resulted in less
inv
expression but did not have a significant effect on invasin levels. However, invasin levels were reduced for strains that harbored
flhDC
on a multicopy plasmid, apparently as a result of increased proteolysis of invasin.
Protection of Gerbils from Amebic Liver Abscess by Vaccination with a 25-mer Peptide Derived from the Cysteine-Rich Region ofEntamoeba histolyticaGalactose-Specific Adherence Lectin
Authors: Lotter Hannelore , Khajawa Fareed , Stanley Samuel L. , Tannich Egbert 
Published: July 2002

ABSTRACTThe protozoan parasiteEntamoeba histolyticacauses extensive morbidity and mortality through intestinal infection and amebic liver abscess. Here we show that immunization of gerbils with a single keyhole limpet hemocyanin-coupled 25-mer peptide derived from the 170-kDa subunit of theE. histolyticagalactose-binding adhesin is sufficient to confer substantial protection against experimentally induced amebic liver abscesses. Vaccination provided total protection in 5 of 15 immunized gerbils, and abscesses were significantly smaller (P< 0.01) in the remaining vaccinated animals. The degree of protection correlated with the titer of antibodies to the peptide, and results of passive transfer experiments performed with SCID mice were consistent with a role for antibodies in protection. In addition, parenteral or oral vaccination of gerbils with 13-amino-acid subfragments of the peptide N-terminally fused to the B subunit of cholera toxin also significantly inhibited liver abscess formation (P< 0.05). These data indicate that small peptides derived from the galactose-binding adhesin administered by the parenteral or oral route can provide protection against amebic liver abscess and should be considered as components of a subunit vaccine against invasive amoebiasis.
Induction of Proinflammatory Cytokines from Human Respiratory Epithelial Cells after Stimulation by NontypeableHaemophilus influenzae
Authors: Clemans Daniel L. , Bauer Richard J. , Hanson Julie A. , Hobbs Monte V. , St. Geme Joseph W. , Marrs Carl F. , Gilsdorf Janet R. 
Published: July 2002

ABSTRACTNontypeableHaemophilus influenzae(NTHi) causes repeated respiratory infections in patients with chronic lung diseases. These infections are characterized by a brisk inflammatory response which results in the accumulation of polymorphonucleated cells in the lungs and is dependent on the expression and secretion of proinflammatory cytokines. We hypothesize that multiple NTHi molecules, including lipooligosaccharide (LOS), mediate cellular interactions with respiratory epithelial cells, leading to the production of proinflammatory cytokines. To address this hypothesis, we exposed 9HTEo− human tracheal epithelial cells to NTHi and compared the resulting profiles of cytokine gene expression and secretion using multiprobe RNase protection assays and enzyme-linked immunosorbent assays (ELISA), respectively. Dose-response experiments demonstrated a maximum stimulation of most cytokines tested, using a ratio of 100 NTHi bacterial cells to 1 9HTEo− tracheal epithelial cell. Compared with purified LOS, NTHi bacterial cells stimulated 3.6- and 4.5-fold increases in epithelial cell expression of interleukin-8 (IL-8) and IL-6 genes, respectively. Similar results were seen with epithelial cell macrophage chemotactic protein 1, IL-1α, IL-1β, and tumor necrosis factor alpha expression. Polymyxin B completely inhibited LOS stimulation but only partially reduced NTHi whole cell stimulation. Taken together, these results suggest that multiple bacterial molecules including LOS contribute to the NTHi stimulation of respiratory epithelial cell cytokine production. Moreover, no correlation was seen between NTHi adherence to epithelial cells mediated by hemagglutinating pili, Hia, HMW1, HMW2, and Hap and epithelial cytokine secretion. These data suggest that bacterial molecules beyond previously described NTHi cell surface adhesins and LOS play a role in the induction of proinflammatory cytokines from respiratory epithelial cells.
Antibody and Cytokine Responses to the Cilium-Associated Respiratory Bacillus in BALB/c and C57BL/6 Mice
Authors: Kendall Lon V. , Riley Lela K. , Hook Reuel R. , Besch-Williford Cynthia L. , Franklin Craig L. 
Published: July 2002

ABSTRACTThe cilium-associated respiratory (CAR) bacillus is a gram-negative, gliding bacterium that causes persistent respiratory tract infections in rodents despite histologic and serologic evidence of a marked immune response. To assess humoral immunity and cytokine responses in CAR bacillus disease, 6-week-old female BALB/c and C57BL/6 mice were inoculated intratracheally with 105CAR bacillus organisms. CAR bacillus-specific serum immunoglobulins (immunoglobulin M [IgM], IgG1, IgG2a, IgG2b, IgG3, and IgA) and local pulmonary cytokines (tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], and interleukin-4 [IL-4]) were evaluated by enzyme-linked immunosorbent assay every 7 days for 49 days. BALB/c mice developed CAR bacillus-induced lesions early in the course of disease that became more severe with time. Correlating with increasing disease severity, BALB/c mice had elevations in all antibody isotypes tested, and elevations in pulmonary TNF-α, IFN-γ, and IL-4. C57BL/6 mice developed mild lesions with mild increases in serum IgM, IgG1, IgG2b, and IgG3 levels and minimally detectable IgG2a and IgA. Cytokine perturbations were not detected in C57BL/6 mice. The persistence of infection in BALB/c mice with vigorous serum antibody responses and increased IFN-γ and IL-4 responses suggests that humoral immunity and T-cell responses are ineffective at preventing CAR bacillus disease. Furthermore, the lackluster antibody responses and undetectable cytokine responses in C57BL/6 mice suggest that humoral immunity and T-cell responses are not critical in resistance to CAR bacillus-induced disease.
Distinct Response Kinetics of Gamma Interferon and Interleukin-4 in Bovine Tuberculosis
Authors: Rhodes S. G. , Palmer N. , Graham S. P. , Bianco A. E. , Hewinson R. G. , Vordermeier H. M. 
Published: July 2002

ABSTRACTThis study shows that gamma interferon (IFN-γ) and interleukin-4 (IL-4) cytokine responses are produced by peripheral blood cells in cattle infected withMycobacterium bovis. The different kinetics of the IFN-γ and IL-4 responses to bovine tuberculin and to ESAT-6 following experimental intratracheal infection withM. bovisare described. An early increase in IFN-γ was observed that was maintained throughout the period studied. In contrast, the IL-4 response was delayed and confined to a peak of activity lasting 6 to 8 weeks. Interestingly, an experimental challenge of cattle with a lower dose ofM. boviswhich did not result in the development of lesions, positive DTH skin test, or substantial IFN-γ responses nevertheless generated strong specific IL-4 responses. Investigation of naturally infectedM. bovisfield reactors showed increased IFN-γ and IL-4 responses compared to uninfected cattle and that both of these cytokines were equally able to differentiate infected from uninfected animals. The magnitude of theM. bovis-induced IL-4 responses were found to be similar to the antigen-specific IL-4 responses of cattle infected with the parasitic nematodeOnchocerca ochengi, further supporting the presence of this type 2 cytokine in bovine tuberculosis.
Absence of a Cysteine Protease Effect on Bacterial Virulence in Two Murine Models of Human Invasive Group A Streptococcal Infection
Authors: Ashbaugh Cameron D. , Wessels Michael R. 
Published: July 2002

ABSTRACT

The cysteine protease of group A streptococci has been suggested to contribute to the pathogenesis of invasive infection through degradation of host tissue, activation of the host inflammatory response, release of protective molecules from the bacterial cell surface, or other mechanisms. However, studies of the effects on virulence of inactivating the cysteine protease gene
speB
have yielded conflicting results. In some reports, a
speB
mutant was relatively avirulent in mouse models of invasive infection whereas little or no attenuation of virulence was observed in other studies of similar mutant strains. Possible reasons for these discordant results include differences in the streptococcal strains from which the
speB
mutants were derived, differences in the infection models employed, or unintended effects on another virulence determinant(s) that arose during the derivation of a
speB
mutant. We attempted to clarify these issues by characterizing the phenotypic properties and relative virulence in mice of two
speB
mutant strains, both derived from wild-type strain AM3:
speB
mutant AM3speB, which has been shown to be markedly attenuated in virulence in mice after intraperitoneal or subcutaneous challenge, and AM3speBΩ, a new mutant strain derived for this investigation. Both mutant strains were negative for protease activity, as expected, and both produced wild-type amounts of type 3 M protein and streptolysin O. However, AM3speB produced significantly less cell-associated hyaluronic acid capsule than did parent strain AM3 or strain AM3speBΩ. Compared to wild-type strain AM3, AM3speB was more sensitive to opsonophagocytic killing in vitro and was significantly less virulent in mice after intraperitoneal challenge. By contrast, AM3speBΩ was fully resistant to phagocytosis and did not differ significantly from the wild-type strain in mouse virulence after an intraperitoneal or subcutaneous challenge. We concluded that previous reports attributing loss of virulence in strain AM3speB to inactivation of
speB
are in error. Within the limitations of the models used, we found no effect of cysteine protease on invasive streptococcal infection.
Comparative Analysis of Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Activity in Serum and Lethality in Mice and Rabbits Pretreated with the Staphylococcal Superantigen Toxic Shock Syndrome Toxin 1
Authors: Dinges Martin M. , Schlievert Patrick M. 
Published: July 2002

ABSTRACTHost susceptibility to lipopolysaccharide (LPS) is correlated with the levels of circulating tumor necrosis factor alpha (TNF-α) that develop in response to circulating LPS. Mice are resistant, relative to rabbits, to the lethal effects of LPS. This study indicates that mice and rabbits are equally sensitive to the lethal effects of circulating TNF-α but that mice are more resistant than rabbits to the induction of circulating TNF-α by LPS.
Brucella abortus
Genes Identified following Constitutive Growth and Macrophage Infection
Authors: Eskra Linda , Canavessi Aurea , Carey Merriann , Splitter Gary 
Published: July 2002

ABSTRACT

The chronicity of
Brucella abortus
infection in humans and animals depends on the organism's ability to escape host defenses by gaining entry and surviving inside the macrophage. Although no human vaccine exists for
Brucella
, vaccine development in other bacteria has been based on deletions of selective nutritional as well as regulatory systems. Our goal is to develop a vaccine for
Brucella
. To further this aim, we have used a green fluorescent protein (GFP) reporter system to identify constitutively and intracellularly induced
B. abortus
genes. Constitutively producing
gfp
clones exhibited sequence homology with genes associated with protein synthesis and metabolism (initiation factor-1 and tRNA ribotransferase) and detoxification (organic hydroperoxidase resistance). Of greater interest, clones negative for constitutively produced
gfp
in agar were examined by fluorescence microscopy to detect promoter activity induced within macrophages 4 and 24 h following infection. Bacterial genes activated in macrophages 4 h postinfection appear to be involved in adapting to intracellular environmental conditions. Included in this group were genes for detoxification (lactoglyglutathione lyase gene), repair (formamidopyrimidine-DNA glycosylase gene), osmotic protection (K
+
transport gene), and site-specific recombination (
xerD
gene). A gene involved in metabolism and biosynthesis (deoxyxylulose 5′ phosphate synthase gene) was also identified. Genes activated 24 h following infection were biosynthesis- and metabolism-associated genes (iron binding protein and rhizopine catabolism). Identification of
B. abortus
genes that are activated following macrophage invasion provides insight into
Brucella
pathogenesis and thus is valuable in vaccine design utilizing selective targeted deletions of newly identified
Brucella
genes.
Mice Lacking Interleukin-2 (IL-2)/IL-15 Receptor β Chain Are Susceptible to Infection with AvirulentSalmonella entericasubsp.entericaSerovar Choleraesuis but Mice Lacking IL-2 Are Resistant
Authors: Nishimura Hitoshi , Tagaya Mitsuhiko , Tsunobuchi Hironaka , Suzuki Haruhiko , Nakashima Izumi , Yoshikai Yasunobu 
Published: July 2002

ABSTRACTInterleukin-2 (IL-2)/IL-15 receptor β (IL-15Rβ)−/−mice were susceptible to infection with avirulentSalmonella entericasubsp.entericaserovar Choleraesuis, whereas IL-2−/−mice were resistant. A natural killer cell response was not evident for both types of deficient mice. A Th1 response was detected in IL-2−/−but not in IL-2/IL-15Rβ−/−mice infected withSalmonella, suggesting that IL-2/IL-15Rβ signaling is important for the generation of protective Th1 cells.
Enhanced Immunogenicity of CD4+T-Cell Responses and Protective Efficacy of a DNA-Modified Vaccinia Virus Ankara Prime-Boost Vaccination Regimen for Murine Tuberculosis
Authors: McShane Helen , Brookes Roger , Gilbert Sarah C. , Hill Adrian V. S. 
Published: July 2002

ABSTRACTDNA vaccines whose DNA encodes a variety of antigens fromMycobacterium tuberculosishave been evaluated for immunogenicity and protective efficacy. CD8+T-cell responses and protection achieved in other infectious disease models have been optimized by using a DNA immunization to prime the immune system and a recombinant virus encoding the same antigen(s) to boost the response. A DNA vaccine (D) and recombinant modified vaccinia virus Ankara (M) in which the DNA encodes early secreted antigenic target 6 and mycobacterial protein tuberculosis 63 synthesized, and each was found to generate specific gamma interferon (IFN-γ)-secreting CD4+T cells. Enhanced CD4+IFN-γ T-cell responses were produced by both D-M and M-D immunization regimens. Significantly higher levels of IFN-γ were seen with a D-D-D-M immunization regimen. The most immunogenic regimens were assessed in a challenge study and found to produce protection equivalent to that produced byMycobacterium bovisBCG. Thus, heterologous prime-boost regimens boost CD4+as well as CD8+T-cell responses, and the use of heterologous constructs encoding the same antigen(s) may improve the immunogenicity and protective efficacy of DNA vaccines against tuberculosis and other diseases.