bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Hypothetical Protein CT813 Is Localized in theChlamydia trachomatisInclusion Membrane and Is Immunogenic in Women Urogenitally Infected withC. trachomatis
Authors: Chen Chaoqun , Chen Ding , Sharma Jyotika , Cheng Wen , Zhong Youmin , Liu Kaiyang , Jensen Jani , Shain Rochelle , Arulanandam Bernard , Zhong Guangming 
Published: July 2006

ABSTRACTUsing antibodies raised with chlamydial fusion proteins, we have localized a protein encoded by hypothetical open reading frame CT813 in the inclusion membrane ofChlamydia trachomatis. The detection of theC. trachomatisinclusion membrane by an anti-CT813 antibody was blocked by the CT813 protein but not unrelated fusion proteins. The CT813 protein was detected as early as 12 h after chlamydial infection and was present in the inclusion membrane during the entire growth cycle. All tested serovars fromC. trachomatisbut not other chlamydial species expressed the CT813 protein. Exogenously expressed CT813 protein in HeLa cells displayed a cytoskeleton-like structure similar to but not overlapping with host cell intermediate filaments, suggesting that the CT813 protein is able to either polymerize or associate with host cell cytoskeletal structures. Finally, women withC. trachomatisurogenital infection developed high titers of antibodies to the CT813 protein, demonstrating that the CT813 protein is not only expressed but also immunogenic during chlamydial infection in humans. In all, the CT813 protein is an inclusion membrane protein unique toC. trachomatisspecies and has the potential to interact with host cells and induce host immune responses during natural infection. Thus, the CT813 protein may represent an important candidate for understandingC. trachomatispathogenesis and developing intervention and prevention strategies for controllingC. trachomatisinfection.
Gamma Interferon Secretion by Human Vγ2Vδ2 T Cells after Stimulation with Antibody against the T-Cell Receptor plus the Toll-Like Receptor 2 Agonist Pam3Cys
Authors: Deetz Carl O. , Hebbeler Andrew M. , Propp Nadia A. , Cairo Cristiana , Tikhonov Illia , Pauza C. David 
Published: July 2006

ABSTRACTCirculating Vγ2Vδ2 T-cell populations in healthy human beings are poised for rapid responses to bacterial or viral pathogens. We asked whether Vγ2Vδ2 T cells use the Toll-like receptor (TLR) family to recognize pathogen-associated molecular pattern molecules and to regulate cell functions. Analysis of expanded Vγ2Vδ2 T-cell lines showed the abundant presence of TLR2 mRNA, implying that these receptors are important for cell differentiation or function. However, multiple efforts to detect TLR2 protein on the cell surface or in cytoplasmic compartments gave inconsistent results. Functional assays confirmed that human Vγ2Vδ2 T cells could respond to the TLR2 agonist (S)-(2,3-bis(palmitoyloxy)-(2RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser(S)-Lys4-OH trihydrochloride (Pam3Cys), but the response required coincident stimulation through the γδ T-cell receptor (TCR). Dually stimulated cells produced higher levels of cytoplasmic or cell-free gamma interferon and showed increased expression of the lysosome-associated membrane protein CD107a on the cell surface. A functional TLR2 that requires coincident TCR stimulation may increase the initial potency of Vγ2Vδ2 T-cell responses at the site of infection and promote the rapid development of subsequent acquired antipathogen immunity.
Signature-Tagged Mutagenesis of
Klebsiella pneumoniae
To Identify Genes That Influence Biofilm Formation on Extracellular Matrix Material
Authors: Boddicker Jennifer D. , Anderson Rebecca A. , Jagnow Jennifer , Clegg Steven 
Published: July 2006

ABSTRACT

Klebsiella pneumoniae
causes urinary tract infections, respiratory tract infections, and septicemia in susceptible individuals. Strains of
Klebsiella
frequently produce extended-spectrum beta-lactamases, and infections with these strains can lead to relatively high mortality rates (approximately 15%). Other virulence factors include production of an antiphagocytic capsule and outer membrane lipopolysaccharide (LPS), which mediates serum resistance, as well as fimbriae on the surface of the bacteria. Type 1 fimbriae mediate adherence to many types of epithelial cells and may facilitate adherence of the bacteria to the bladder epithelium. Type 3 fimbriae can bind in vitro to the extracellular matrix of urinary and respiratory tissues, suggesting that they mediate binding to damaged epithelial surfaces. In addition, type 3 fimbriae are required for biofilm formation by
Klebsiella pneumoniae
on plastics and human extracellular matrix; thus, they may facilitate the formation of treatment-resistant biofilm on indwelling plastic devices, such as catheters and endotracheal tubing. The presence of these devices may cause tissue damage, allowing
Klebsiella
to grow as a biofilm on exposed tissue basement membrane components. Though in vivo biofilm growth may be an important step in the infection process, little is known about the genetic factors required for biofilm formation by
Klebsiella pneumoniae
. Thus, we performed signature-tagged mutagenesis to identify factors produced by
K. pneumoniae
strain 43816 that are required for biofilm formation. We identified mutations in the
cps
capsule gene cluster, previously unidentified transcriptional regulators, fimbrial, and sugar phosphotransferase homologues, as well as genetic loci of unknown function, that affect biofilm formation.
Intranasal Immunization with the Cholera Toxin B Subunit-Pneumococcal Surface Antigen A Fusion Protein Induces Protection against Colonization with
Streptococcus pneumoniae
and Has Negligible Impact on the Nasopharyngeal and Oral Microbiota of Mice
Authors: Pimenta F. C. , Miyaji E. N. , Arêas A. P. M. , Oliveira M. L. S. , de Andrade A. L. S. S. , Ho P. L. , Hollingshead S. K. , Leite L. C. C. 
Published: July 2006

ABSTRACT

One of the candidate proteins for a mucosal vaccine antigen against
Streptococcus pneumoniae
is PsaA (pneumococcal surface antigen A). Vaccines targeting mucosal immunity may raise concerns as to possible alterations in the normal microbiota, especially in the case of PsaA, which was shown to have homologs with elevated sequence identity in other viridans group streptococci. In this work, we demonstrate that intranasal immunization with a cholera toxin B subunit-PsaA fusion protein is able to protect mice against colonization with
S. pneumoniae
but does not significantly alter the natural oral or nasopharyngeal microbiota of mice.
Cardiac Failure in C5-Deficient A/J Mice afterCandida albicansInfection
Authors: Mullick Alaka , Leon Zully , Min-Oo Gundula , Berghout Joanne , Lo Rita , Daniels Eugene , Gros Philippe 
Published: July 2006

ABSTRACTThe effect of a deficiency in the C5 component of complement on the pathophyisology of infection with the fungal pathogenCandida albicanswas studied by using the A/J inbred mouse strain and the BcA17 congenic mouse strain. Acute infection caused by intravenous injection ofC. albicansblastospores is associated with rapid fungal replication in the heart, brain, and, in particular, kidneys of C5-deficient mice. Histological studies and analysis of markers for tissue damage indicated that the heart is the organ that is most affected and that it ultimately fails in C5-deficient mice. In A/J and BcA17 mice, tissue damage is associated with (i) cellular infiltration in the heart, which is not seen in the kidney despite the higher fungal load in the latter organ, and (ii) a very strong inflammatory response, including elevated levels of many cytokines and chemokines. This results in cardiomyopathy, which is associated with elevated levels of creatine kinase and cardiac troponin I in the circulation. Damage to the cardiac muscle is associated with metabolic changes, including hypoglycemia, decreased lipid utilization resulting in elevated levels of cardiac triglycerides, and unproductive glucose utilization linked to a dramatic increase in the level of pyruvate dehydrogenase kinase 4 (Pdk4), a negative regulator of the pyruvate dehydrogenase complex.
Regulation of Production of Mucosal Antibody to Pneumococcal Protein Antigens by T-Cell-Derived Gamma Interferon and Interleukin-10 in Children
Authors: Zhang Qibo , Bernatoniene Jolanta , Bagrade Linda , Paton James C. , Mitchell Timothy J. , Hammerschmidt Sven , Nunez Desmond A. , Finn Adam 
Published: July 2006

ABSTRACTNasopharyngeal tonsils (adenoids) are part of human nasopharynx-associated lymphoid tissue, which may play an important role in local defense against pneumococci. Recent studies with animals have suggested that several pneumococcal proteins, including CbpA and pneumolysin (Ply), may be vaccine candidates. Our recent data obtained with children suggest that antibodies to these proteins may protect against carriage. This study was performed to investigate the regulation of the T-cell-dependent antibody responses to CbpA and pneumolysin by cytokines in adenoidal immune cells from children. Adenoidal mononuclear cells (MNC) were cultured with pneumococcal concentrated culture supernatants (CCS) or recombinant proteins. Cytokine expression profiles in adenoidal MNC after antigen stimulation were analyzed by reverse transcription-PCR, protein array analysis, and an immunoassay, along with an antibody production analysis. The roles, interactions, and cellular sources of the main cytokines identified were evaluated further. Pneumococcal CCS induced production of CbpA- and Ply-specific antibodies in association with several chemokines and cytokines, including gamma interferon (IFN-γ) and interleukin-10 (IL-10) in MNC. The antibody production correlated well with the concentrations of these two cytokines. Addition of recombinant IFN-γ or IL-10 enhanced antibody production, and monoclonal antibodies to these two cytokines and T-cell depletion significantly reduced antibody production. Intracellular cytokine staining showed that T cells are a major source of IFN-γ and IL-10. Recombinant Ply and, to a lesser extent, recombinant CbpA induced significant production of IFN-γ and IL-10 in MNC. T-cell-derived IFN-γ and IL-10 may be key regulators of production of mucosal antibody to pneumococcal protein antigens in the nasopharynx and may play an important role in local protection against pneumococcal infection in children.
Staphyloxanthin Plays a Role in the Fitness of
Staphylococcus aureus
and Its Ability To Cope with Oxidative Stress
Authors: Clauditz Alexandra , Resch Alexandra , Wieland Karsten-Peter , Peschel Andreas , Götz Friedrich 
Published: July 2006

ABSTRACT

Staphyloxanthin is a membrane-bound carotenoid of
Staphylococcus aureus
. Here we studied the interaction of staphyloxanthin with reactive oxygen substances (ROS) and showed by comparative analysis of the wild type (WT) and an isogenic
crtM
mutant that the WT is more resistant to hydrogen peroxide, superoxide radical, hydroxyl radical, hypochloride, and neutrophil killing.
Unique Features of a Highly Pathogenic
Campylobacter jejuni
Strain
Authors: Hofreuter Dirk , Tsai Jennifer , Watson Robert O. , Novik Veronica , Altman Bill , Benitez Michelle , Clark Christina , Perbost Clotilde , Jarvie Thomas , Du Lei , Galán Jorge E. 
Published: July 2006

ABSTRACT

Campylobacter jejuni
, a major human enteric pathogen, exhibits significant strain-to-strain differences which result in differences in pathogenic potential.
C. jejuni
81-176 is a highly virulent strain that exhibits unique pathogenic features and is used by many research laboratories. We have determined the nucleotide sequence of its genome and compared it to the genomes of other sequenced
C. jejuni
strains. We identified a number of unique genetic features which may confer specific metabolic and pathogenic properties on this strain. We have also identified regions of the
C. jejuni
genome that are hot spots for the integration of horizontally acquired genetic material. This information should help the understanding of the pathogenesis of
C. jejuni
and, in particular, the unique features of this highly pathogenic strain.
Effect of Lung Surfactant Collectins on Bronchoalveolar Macrophage Interaction withBlastomyces dermatitidis: Inhibition of Tumor Necrosis Factor Alpha Production by Surfactant Protein D
Authors: Lekkala Madhavi , LeVine Ann Marie , Linke Michael J. , Crouch Erika C. , Linders Bruce , Brummer Elmer , Stevens David A. 
Published: July 2006

ABSTRACTAlveolar surfactant modulates the antimicrobial function of bronchoalveolar macrophages (BAM). Little is known about the effect of surfactant-associated proteins in bronchoalveolar lavage fluid (BALF) on the interaction of BAM andBlastomyces dermatitidis. We investigated BALF enhancement or inhibition of TNF-α production by BAM stimulated byB. dermatitidis. BAM from CD-1 mice were stimulated withB. dermatitidiswithout or with normal BALF, surfactant protein A-deficient (SP-A−/−) or surfactant protein D-deficient (SP-D−/−) BALF, or a mixture of SP-A−/−and SP-D−/−BALF. An enzyme-linked immunosorbent assay was used to measure tumor necrosis factor alpha (TNF-α) in culture supernatants. BALFs were standardized in protein concentration. BAM plusB. dermatitidis(BAM-B. dermatitidis) TNF-α production was inhibited ≥47% by BALF or SP-A−/−BALF (at 290 or 580 μg of protein/ml,P< 0.05 to 0.01); in contrast, SP-D−/−BALF did not significantly inhibit TNF-α production. If SP-A−/−BALF was mixed in equal amounts with SP-D−/−BALF, TNF-α production by BAM-B. dermatitidiswas inhibited (P< 0.01). Finally, pure SP-D added to SP-D−/−BALF inhibited TNF-α production by BAM-B. dermatitidis(P< 0.01).B. dermatitidisincubated with BALF and washed, plus BAM, stimulated 63% less production of TNF-α than did unwashedB. dermatitidis(P< 0.05). SP-D was detected by anti-SP-D antibody on BALF-treated unwashedB. dermatitidisin an immunofluorescence assay (IFA). The BALF depleted by a coating ofB. dermatitidislost the ability to inhibit TNF-α production (P < 0.05). 1,3-β-Glucan was a good stimulator of BAM for TNF-α production and was detected onB. dermatitidisby IFA. β-Glucan incubated with BALF inhibited the binding of SP-D in BALF toB. dermatitidisas demonstrated by IFA. Our data suggest that SP-D in BALF binds β-glucan onB. dermatitidis, blocking BAM access to β-glucan, thereby inhibiting TNF-α production. Thus, whereas BALF constituents commonly mediate antimicrobial activity,B. dermatitidismay utilize BALF constituents, such as SP-D, to blunt the host defensive reaction; this effect could reduce inflammation and tissue destruction but could also promote disease.
An Intradermal Environment Promotes a Protective Type-1 Response against Lethal Systemic Monocytotropic Ehrlichial Infection
Authors: Stevenson Heather L. , Jordan Jeffrey M. , Peerwani Ziad , Wang Hui-Qun , Walker David H. , Ismail Nahed 
Published: July 2006

ABSTRACT

Immune responses against monocytotropic ehrlichiosis during infection with a strain of
Ehrlichia
from
Ixodes ovatus
(IOE) were evaluated using a model that closely reproduces the pathology and immunity associated with tick-transmitted human monocytotropic ehrlichiosis. C57BL/6 mice were inoculated intradermally or intraperitoneally with high-dose highly virulent IOE or intraperitoneally with mildly virulent
Ehrlichia muris
. Intradermal (i.d.) infection with IOE established mild, self-limited disease associated with minimal hepatic apoptosis, and all mice survived past 30 days. Intraperitoneal (i.p.) infection with IOE resulted in acute, severe toxic shock-like syndrome and severe multifocal hepatic apoptosis and necrosis, and all mice succumbed to disease. Compared to i.p. infection with IOE, intradermally infected mice had a 100- to 1,000-fold lower bacterial load in the spleen with limited dissemination. Compared to mice infected intraperitoneally with IOE, i.d. infection stimulated a stronger protective type-1 cell-mediated response on day 7 of infection, characterized by increased percentages of both CD4
+
and CD8
+
splenic T cells, generation of a greater number of IOE-specific, gamma interferon-producing CD4
+
Th1 cells, and higher levels of tumor necrosis factor (TNF-α) in the spleen but lower concentrations of serum TNF-α and interleukin-10. These data suggest that under the conditions of natural route of challenge (i.e., i.d. inoculation), the immune response has the capacity to confer complete protection against monocytotropic ehrlichiosis, which is associated with a strong cell-mediated type-1 response and decreased systemic production of pro- and anti-inflammatory cytokines.
The
yjeQ
Gene Is Required for Virulence of
Staphylococcus aureus
Authors: Campbell Tracey L. , Henderson James , Heinrichs David E. , Brown Eric D. 
Published: July 2006

ABSTRACT

Gene products required for in vivo growth and survival of
Staphylococcus aureus
and other pathogens represent new targets for antimicrobial chemotherapy. In this study we created a
Staphylococcus aureus yjeQ
deletion strain and tested its virulence using a mouse kidney abscess infection model. The
yjeQ
deletion strain was compromised for growth in vitro and severely attenuated for virulence. We concluded that
yjeQ
is an attractive and novel new drug target.
Characterization of the T-Cell Receptor Vβ Repertoire in the Human Immune Response againstLeishmaniaParasites
Authors: Clarêncio Jorge , de Oliveira Camila I. , Bomfim Glória , Pompeu Margarida M. , Teixeira Maria Jania , Barbosa Theolis C. , Souza-Neto Sebastião , Carvalho Edgar M. , Brodskyn Cláudia , Barral Aldina , Barral-Netto Manoel 
Published: July 2006

ABSTRACTIn order to explore a possible presence of hyperreactive T-cell clones in human cutaneous leishmaniasis (CL), we have investigated, by flow cytometry, the expression of Vβ chains of T-cell receptors (TCRs) in the following types of cells: (i) peripheral blood mononuclear cells (PBMCs) from CL patients, which were then compared to those from normal volunteers; (ii) unstimulated and solubleLeishmaniaantigen-stimulated draining lymph node cells from CL patients; (iii) PBMCs from volunteers before versus afterLeishmaniaimmunization; and (iv) PBMCs from healthy volunteers that were primed in vitro with liveLeishmaniaparasites. Our results show a modulation in the TCR Vβ repertoire during CL and after antigen stimulation of patients' cells. Vaccination, however, leads to a broad expansion of different Vβ TCRs. We also observed an association between TCR Vβ12 expression, T-cell activation, and gamma interferon production upon in vitro priming withLeishmania.Collectively, these results both indicate that infection with live parasites or exposure to parasite antigen can modulate the TCR Vβ repertoire and suggest that TCR Vβ12 may be implicated in the response toLeishmania.
The Circadian ClockPeriod 2Gene Regulates Gamma Interferon Production of NK Cells in Host Response to Lipopolysaccharide-Induced Endotoxic Shock
Authors: Liu Jianguo , Mankani Guantham , Shi Xiaoyan , Meyer Mark , Cunningham-Runddles Susana , Ma Xiaojing , Sun Zhong Sheng 
Published: July 2006

ABSTRACTThePeriod 2(Per2) gene is a key molecular component in controlling mammalian circadian rhythms at the levels of gene expression, physiology, and pathogenesis. Although many immune parameters, such as the number of different subtypes of circulating immune cells and the level of cytokine production in response to infection with bacteria and viruses, have been well documented to display a circadian pattern in mammals, the basic features of molecular clock components in the immune system and the role of clock genes in regulating host immune defenses remain uncharacterized. Previously, we have reported that circadian clock genes oscillate in human mononuclear cells. Here we report that Per2-deficient mice were more resistant to lipopolysaccharide (LPS)-induced endotoxic shock than control wild-type mice. We further demonstrate that the levels of the proinflammatory cytokines gamma interferon (IFN-γ) and interleukin-1β (IL-1β) in the serum were dramatically decreased inPer2−/−mice following LPS challenge, while production of tumor necrosis factor alpha, IL-6, and IL-10 was approximately normal, compared to that in control wild-type mice. Flow cytometric analyses confirmed that the cellularity of most of the immune cell subsets in the spleens of LPS-challenged mice was normal and that the impaired IFN-γ production inPer2−/−mice was attributable to defective NK and NKT cell function. Our data suggest that Per2 is an important regulator of NK cell function, therefore providing the first direct link between the circadian clock system and innate immune responses.
Regulation of Murine Dendritic Cell Immune Responses byHelicobacter felisAntigen
Authors: Drakes Maureen L. , Czinn Steven J. , Blanchard Thomas G. 
Published: July 2006

ABSTRACTHelicobacterinfections are present in approximately 50% of humans, causing severe illnesses such as gastritis and malignancies. Dendritic cells (DC) are critical antigen-presenting cells which link innate and adaptive immune responses. The mechanism of dendritic cell regulation inHelicobacter-induced gastritis is poorly understood. These studies characterized DC isolated from the lamina propria ofHelicobacter-infected mice and analyzed innate and adaptive immune responses elicited byHelicobacterantigen (Ag)-pulsed DC. The presence of DC was elevated in the gastric lamina propria infiltrate of infected mice in comparison with controls. After treatment withHelicobacter felisAg, DC were polarized to secrete interleukin-6 as the dominant cytokine. In the presence of DC andHelicobacterAg, responder allogeneic T cells in culture exhibited limited cell division. We suggest that the response of DC and T cells toHelicobacterAg is critical to the chronic persistence ofHelicobacter-induced gastritis.
The Presence of Peptidoglycan
O
-Acetyltransferase in Various Staphylococcal Species Correlates with Lysozyme Resistance and Pathogenicity
Authors: Bera Agnieszka , Biswas Raja , Herbert Silvia , Götz Friedrich 
Published: July 2006

ABSTRACT

Human-pathogenic bacteria that are able to cause persistent infections must have developed mechanisms to resist the immune defense system. Lysozyme, a cell wall-lytic enzyme, is one of the first defense compounds induced in serum and tissues after the onset of infection. Recently, we showed that
Staphylococcus aureus
is resistant to lysozyme by O acetylating its peptidoglycan (PG) by
O
-acetyltransferase (OatA). We asked the question of which staphylococcal species PG is O acetylated. We applied various methods, such as genome analysis, PCR, Southern blotting, lysozyme sensitivity assay, and verification of O acetylation of PG by high-performance liquid chromatography (HPLC) analysis. PCR analysis using
S. aureus
-derived
oatA
primers and Southern blotting did not yield reliable results with other staphylococcal species. Therefore, we used the HPLC-based assay to directly detect PG O acetylation. Our studies revealed that the muramic acid was O acetylated only in pathogenic, lysozyme-resistant staphylococci (e.g.,
S. aureus
,
S. epidermidis
,
S. lugdunensis
, and others). All nonpathogenic species were lysozyme sensitive. They can be divided into sensitive species (e.g.,
S. carnosus
,
S. gallinarum
, and
S. xylosus
) and hypersensitive species (e.g.,
S. equorum
,
S. lentus
, and
S. arlettae
). In all lysozyme-sensitive species, the analyzed PG was de-O-acetylated. When we transformed the
oatA
gene from lysozyme-resistant
S. aureus
into
S. carnosus
, the corresponding transformants also became lysozyme resistant.