bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence that Tight Junctions Are Disrupted Due to Intimate Bacterial Contact and Not Inflammation during Attaching and Effacing Pathogen Infection In Vivo
Authors: Guttman Julian A. , Samji Fereshte N. , Li Yuling , Vogl A. Wayne , Finlay B. Brett 
Published: October 2006

ABSTRACTIt is widely accepted that tight junctions are altered during infections by attaching and effacing (A/E) pathogens. These disruptions have been demonstrated both in vitro and more recently in vivo. For in vivo experiments, the murine model of A/E infection withCitrobacter rodentiumis the animal model of choice. In addition to effects on tight junctions, these bacteria also colonize the colon at high levels, efface colonocyte microvilli, and cause hyperplasia and inflammation. Although we have recently demonstrated that tight junctions are disrupted byC. rodentium, the issue of direct effects of bacteria on epithelial cell junctions versus the indirect effects of inflammation still remains to be clarified. Here, we demonstrate that during theC. rodentiuminfections, inflammation plays no discernible role in the alteration of tight junctions. The distribution of the tight junction proteins, claudin-1, -3, and -5, are unaffected in inflamed colon, and junctions appear morphologically unaltered when viewed by electron microscopy. Additionally, tracer molecules are not capable of penetrating the inflamed colonic epithelium of infected mice that have cleared the bacteria. Finally, infected colonocytes from mice exposed toC. rodentiumfor 14 days, which have high levels of bacterial attachment to colonocytes as well as inflammation, have characteristic, altered claudin localization whereas cells adjacent to infected colonocytes retain their normal claudin distribution. We conclude that inflammation plays no discernible role in tight junction alteration during A/E pathogenesis and that tight junction disruption in vivo appears dependent only on the direct intimate attachment of the pathogenic bacteria to the cells.
Amino Acid Residues within EnterohemorrhagicEscherichia coliO157:H7 Tir Involved in Phosphorylation, α-Actinin Recruitment, and Nck-Independent Pedestal Formation
Authors: Allen-Vercoe Emma , Waddell Barbara , Toh Michael C. W. , DeVinney Rebekah 
Published: October 2006

ABSTRACTEnterohemorrhagicEscherichia coli(EHEC) O157:H7 and enteropathogenicE. coli(EPEC) adherence to epithelial cells results in the formation of actin pedestals. Pedestal formation requires the bacterial protein Tir, which is inserted into the epithelial cell plasma membrane by the type III secretion system. EPEC and EHEC use different Tir-based mechanisms for pedestal formation, and the EPEC Tir residues required have been well described. In contrast, little is known about the regions of EHEC O157:H7 Tir that are essential for pedestal formation. Additionally, EHEC O157:H7 Tir is serine/threonine phosphorylated, although the residues involved and their role in pedestal formation are not known. In this study, we describe two regions within the carboxy terminus of EHEC O157:H7 Tir that are required for phosphorylation and pedestal formation. Serines 436 and 437 are substrates for protein kinase A phosphorylation, although this is not required to form pedestals. Using a series of internal deletion mutants, we found that amino acids 454 to 463 are required for efficient pedestal formation. Deleting this region resulted in a significant decrease in the recruitment of both filamentous actin and the actin binding protein α-actinin. As α-actinin binds directly to the EHEC O157:H7 amino terminus, these data suggest that its recruitment is dependent on pedestal formation.
Spontaneous Recovery of Pathogenicity by
Leishmania major hsp100
−
/
−
Alters the Immune Response in Mice
Authors: Reiling Linda , Jacobs Thomas , Kroemer Manfred , Gaworski Iris , Graefe Sebastian , Clos Joachim 
Published: October 2006

ABSTRACT

By using repeated mouse infection cycles, we obtained an escape variant with restored infectivity and pathogenicity that originated from a single, noninfectious
hsp100
−
/
−
gene (formerly known as Δ
clpB
) replacement clone of
Leishmania major
, the causative agent of cutaneous leishmaniasis. This isolate elicited increased infiltration of immune cells to the site of infection and altered the polarization of the immune response in BALB/c mice from a predominantly TH2 type to a TH1 type. A clonal analysis resulted in isolation of two clones with antagonistic properties. While one clone exhibited restored infectivity in isolated macrophages but caused no persistent infection in the mouse model, the second clone was unable to infect macrophages in vitro but could establish a lasting infection and form progressive lesions in BALB/c mice. Our results add to the evidence that the TH1-TH2 dichotomy of the early immune response against
L. major
not only depends on the genetic predisposition of the host but also depends on intrinsic properties of the parasite.
Early Gamma Interferon and Interleukin-2 Responses to Vaccination Predict the Late Resting Memory in Malaria-Naïve and Malaria-Exposed Individuals
Authors: Bejon Philip , Keating Sheila , Mwacharo Jedidah , Kai Oscar K. , Dunachie Susanna , Walther Michael , Berthoud Tamara , Lang Trudie , Epstein Judy , Carucci Daniel , Moris Philippe , Cohen Joe , Gilbert Sarah C. , Peshu Norbert , Marsh Kevin , Hill Adrian V. S. 
Published: October 2006

ABSTRACT
Two different cell populations respond to potent T-cell-inducing vaccinations. The induction and loss of effector cells can be seen using an ex vivo enzyme-linked immunospot (ELISPOT) assay, but the more durable resting memory response is demonstrable by a cultured ELISPOT assay. The relationship of the early effector response to durable resting memory is incompletely understood. Effector phenotype is usually identified by gamma interferon (IFN-γ) production, but interleukin-2 (IL-2) has been specifically linked to the differentiation of memory cells. Here, IFN-γ- and IL-2-secreting effector cells were identified by an ex vivo ELISPOT assay 1 week after vaccination and compared with the resting memory responses detected by a cultured ELISPOT assay 3 months later. The different kinetics and induction of IL-2 by different vaccines and natural exposure are described. Furthermore, both early IFN-γ and IL-2 production independently predicted subsequent memory responses at 3 months in malaria-naïve volunteers, but only IFN-γ predicted memory in malaria-exposed volunteers. However, dual ELISPOT assays were also performed on malaria-exposed volunteers to identify cells producing both cytokines simultaneously. This demonstrated that double-cytokine-producing cells were highly predictive of memory. This assay may be useful in predicting vaccinations most likely to generate stable, long-term memory responses.
Localization of the Hypothetical Protein Cpn0797 in the Cytoplasm of
Chlamydia pneumoniae
-Infected Host Cells
Authors: Dong Feng , Flores Rhonda , Chen Ding , Luo Jianhua , Zhong Youmin , Wu Zhongming , Zhong Guangming 
Published: October 2006

ABSTRACT

Using antibodies raised with chlamydial fusion proteins, we have localized a protein encoded by the hypothetical open reading frame Cpn0797 in the cytoplasm of
Chlamydia pneumoniae
-infected host cells. The anti-Cpn0797 antibodies specifically recognized Cpn0797 protein without cross-reacting with either CPAFcp or Cpn0796, the only two proteins known to be secreted into the host cell cytosol by
C. pneumoniae
organisms. Thus, Cpn0797 represents the third
C. pneumoniae
protein secreted into the host cell cytosol experimentally identified so far.
Tumor Necrosis Factor Alpha- and Inducible Nitric Oxide Synthase-Producing Dendritic Cells Are Rapidly Recruited to the Bladder in Urinary Tract Infection but Are Dispensable for Bacterial Clearance
Authors: Engel Daniel , Dobrindt Ulrich , Tittel André , Peters Petra , Maurer Juliane , Gütgemann Ines , Kaissling Brigitte , Kuziel William , Jung Steffen , Kurts Christian 
Published: October 2006

ABSTRACT

The role of dendritic cells (DC) in urinary tract infections (UTI) is unknown. These cells contribute directly to the innate defense against various viral and bacterial infections. Here, we studied their role in UTI using an experimental model induced by transurethral instillation of the uropathogenic
Escherichia coli
(UPEC) strain 536 into C57BL/6 mice. While few DC were found in the uninfected bladder, many had been recruited after 24 h, mostly to the submucosa and uroepithelium. They expressed markers of activation and maturation and exhibited the CD11b
+
F4/80
+
CD8
−
Gr-1
−
myeloid subtype. Also, tumor necrosis factor alpha (TNF-α)- and inducible nitric oxide synthase (iNOS)-producing CD11b
INT
DC (Tip-DC) were detected, which recently were proposed to be critical in the defense against bacterial infections. However, Tip-DC-deficient CCR2
−/−
mice did not show reduced clearance of UPEC from the infected bladder. Moreover, clearance was also unimpaired in CD11c-DTR mice depleted of all DC by injection of diphtheria toxin. This may be explained by the abundance of granulocytes and of iNOS- and TNF-α-producing non-DC that were able to replace Tip-DC functionality. These findings demonstrate that some of the abundant DC recruited in UTI contributed innate immune effector functions, which were, however, dispensable in the microenvironment of the bladder.
Mycobacterium marinum
Infection of Adult Zebrafish Causes Caseating Granulomatous Tuberculosis and Is Moderated by Adaptive Immunity
Authors: Swaim Laura E. , Connolly Lynn E. , Volkman Hannah E. , Humbert Olivier , Born Donald E. , Ramakrishnan Lalita 
Published: October 2006

ABSTRACT

The zebrafish, a genetically tractable model vertebrate, is naturally susceptible to tuberculosis caused by
Mycobacterium marinum
, a close genetic relative of the causative agent of human tuberculosis,
Mycobacterium tuberculosis
. We previously developed a zebrafish embryo-
M. marinum
infection model to study host-pathogen interactions in the context of innate immunity. Here, we have constructed a flowthrough fish facility for the large-scale longitudinal study of
M. marinum
-induced tuberculosis in adult zebrafish where both innate and adaptive immunity are operant. We find that zebrafish are exquisitely susceptible to
M. marinum
strain M. Intraperitoneal injection of five organisms produces persistent granulomatous tuberculosis, while the injection of ∼9,000 organisms leads to acute, fulminant disease. Bacterial burden, extent of disease, pathology, and host mortality progress in a time- and dose-dependent fashion. Zebrafish tuberculous granulomas undergo caseous necrosis, similar to human tuberculous granulomas. In contrast to mammalian tuberculous granulomas, zebrafish lesions contain few lymphocytes, calling into question the role of adaptive immunity in fish tuberculosis. However, like
rag1
mutant mice infected with
M. tuberculosis
, we find that
rag1
mutant zebrafish are hypersusceptible to
M. marinum
infection, demonstrating that the control of fish tuberculosis is dependent on adaptive immunity. We confirm the previous finding that
M. marinum
ΔRD1 mutants are attenuated in adult zebrafish and extend this finding to show that ΔRD1 predominantly produces nonnecrotizing, loose macrophage aggregates. This observation suggests that the macrophage aggregation defect associated with ΔRD1 attenuation in zebrafish embryos is ongoing during adult infection.
Disparate Immunoregulatory Potentials for Double-Negative (CD4−CD8−) αβ and γδ T Cells from Human Patients with Cutaneous Leishmaniasis
Authors: Antonelli Lis R. V. , Dutra Walderez O. , Oliveira Ricardo R. , Torres Karen C. L. , Guimarães Luiz H. , Bacellar Olivia , Gollob Kenneth J. 
Published: October 2006

ABSTRACTAlthough most T lymphocytes express the αβ T-cell receptor and either CD4 or CD8 molecules, a small population of cells lacking these coreceptors, CD4−CD8−(double negative [DN]) T cells, has been identified in the peripheral immune system of mice and humans. To better understand the role that this population may have in the human immune response againstLeishmaniaspp., a detailed study defining the activation state, cytokine profile, and the heterogeneity of DN T cells bearing αβ or γδ T-cell receptors was performed with a group of well-defined cutaneous leishmaniasis patients. Strikingly, on average 75% of DN T cells from cutaneous leishmaniasis patients expressed the αβ T-cell receptor, with the remainder expressing the γδ receptor, while healthy donors displayed the opposite distribution with ∼75% of the DN T cells expressing the γδ T-cell receptor. Additionally, αβ DN T cells from cutaneous leishmaniasis patients are compatible with previous antigen exposure and recent activation. Moreover, while αβ DN T cells fromLeishmania-infected individuals present a proinflammatory cytokine profile, γδ DN T cells express a regulatory profile exemplified by interleukin-10 production. The balance between these subpopulations could allow for the formation of an effective cellular response while limiting its pathogenic potential.
Immunization with LiveNeisseria lactamicaProtects Mice against Meningococcal Challenge and Can Elicit Serum Bactericidal Antibodies
Authors: Li Yanwen , Zhang Qian , Winterbotham Megan , Mowe Eva , Gorringe Andrew , Tang Christoph M. 
Published: October 2006

ABSTRACTNatural immunity againstNeisseria meningitidisis thought to develop following nasopharyngeal colonization with this bacterium or other microbes expressing cross-reactive antigens.Neisseria lactamicais a commensal of the upper respiratory tract which is often carried by infants and young children; epidemiological evidence indicates that colonization with this bacterium can elicit serum bactericidal activity (SBA) againstNeisseria meningitidis, the most validated correlate of protective immunity. Here we demonstrate experimentally that immunization of mice with liveN. lactamicaprotects animals against lethal meningococcal challenge and that some, but not all, strains ofN. lactamicaelicit detectable SBA in immunized animals regardless of the serogroup ofN. meningitidis. While it is unlikely that immunization with liveN. lactamicawill be implemented as a vaccine against meningococcal disease, understanding the basis for the induction of cross-protective immunity and SBA should be valuable in the design of subunit vaccines for the prevention of this important human infection.
Incidence of hand eczema in female Swedish hairdressers
Authors: Lind Marie-Louise , Albin Maria , Brisman Jonas , Kronholm Diab Kerstin , Lillienberg Linnéa , Mikoczy Zoli , Nielsen Jörn , Rylander Lars , Torén Kjell , Meding Birgitta 
Published: October 2006

Objective:To estimate the occurrence of hand eczema in hairdressers in Sweden.Methods:The occurrence of hand eczema was estimated in a Swedish longitudinal retrospective cohort study including all female graduates from vocational schools for hairdressers from 1970 to 1995. A stratified sample from the general population acted as controls. A self-administered questionnaire including questions on the occurrence of hand eczema, skin atopy, working periods and number of hair treatments performed per week was sent to the participants. Incidence rate ratios (IRRs) of hand eczema were estimated.Results:The incidence rate of hand eczema in hairdressers was 23.8 cases/1000 person-years, whereas in hairdressers who were aged <25 years it was 37.1/1000 person-years. The corresponding IRR for hairdressers compared with controls was 2.5 (95% confidence interval (CI) 2.2 to 2.8), and that for younger hairdressers was 3.1 (95% CI 2.6 to 3.5). The mean age at onset of hand eczema was 21.6 years for hairdressers and 21.2 years for controls. The 1-year prevalence of hand eczema was 18.0% for hairdressers and 12.1% for controls. A large number of hair treatments involving exposure to skin irritants and sensitisers were reported. The incidence rate of hand eczema was higher among individuals with a history of childhood eczema, both for hairdressers and for controls, giving an (age-adjusted) IRR of 1.9 and 2.2, respectively. The attributable fraction of hand eczema from skin atopy was 9.6%. A synergistic effect of skin atopy and hairdressing was found on the occurrence of hand eczema. The relative excess risk due to interaction was 1.21 (95% CI 0.21 to 2.21; p = 0.01).Conclusion:Hairdressers are highly exposed to skin-damaging substances. The self-reported incidence of hand eczema was substantially higher in female hairdressers than in controls from the general population and than that found previously in register-based studies. For many individuals, onset of hand eczema occurs early in life. Only about 10% of the hand eczema cases among hairdressers would be prevented if no one with skin atopy entered the trade.
Occupational exposure to asbestos and man-made vitreous fibres and risk of lung cancer: a multicentre case-control study in Europe
Authors: Carel Rafael , Olsson Ann C , Zaridze David , Szeszenia-Dabrowska Neonila , Rudnai Peter , Lissowska Jolanta , Fabianova Eleonora , Cassidy Adrian , Mates Dana , Bencko Vladimir , Foretova Lenka , Janout Vladimir , Fevotte Joelle , Fletcher Tony , Mannetje Andrea ’t , Brennan Paul , Boffetta Paolo 
Published: October 2006

Objectives:To investigate the contribution of occupational exposure to asbestos and man-made vitreous fibres (MMVF) to lung cancer in high-risk populations in Europe.Methods:A multicentre case-control study was conducted in six Central and Eastern European countries and the UK, during the period 1998–2002. Comprehensive occupational and sociodemographic information was collected from 2205 newly diagnosed male lung cancer cases and 2305 frequency matched controls. Odds ratios (OR) of lung cancer were calculated after adjusting for other relevant occupational exposures and tobacco smoking.Results:The OR for asbestos exposure was 0.92 (95% CI 0.73 to 1.15) in Central and Eastern Europe and 1.85 (95% CI 1.07 to 3.21) in the UK. Similar ORs were found for exposure to amphibole asbestos. The OR for MMVF exposure was 1.23 (95% CI 0.88 to 1.71) with no evidence of heterogeneity by country. No synergistic effect either between asbestos and MMVF or between any of them and smoking was found.Conclusion:In this large community-based study occupational exposure to asbestos and MMVF does not appear to contribute to the lung cancer burden in men in Central and Eastern Europe. In contrast, in the UK the authors found an increased risk of lung cancer following exposure to asbestos. Differences in fibre type and circumstances of exposure may explain these results.
Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor
Authors: Wada Yumiko , Lu Rongzhen , Zhou Dan , Chu John , Przewloka Teresa , Zhang Shijie , Li Long , Wu Yaming , Qin June , Balasubramanyam Vishwasenani , Barsoum James , Ono Mitsunori 
Published: October 2006

AbstractThe interleukin-12 (IL-12) cytokine induces the differentiation of naive T cells to the T helper cell type 1 (Th1) phenotype and is integral to the pathogenesis of Th1-mediated immunologic disorders. A more recently discovered IL-12 family member, IL-23, shares the p40 protein subunit with IL-12 and plays a critical role in the generation of effector memory T cells and IL-17–producing T cells. We introduce a novel compound, STA-5326, that down-regulates both IL-12 p35 and IL-12/IL-23 p40 at the transcriptional level, and inhibits the production of both IL-12 and IL-23 cytokines. Oral administration of STA-5326 led to a suppression of the Th1 but not Th2 immune response in mice. In vivo studies using a CD4+CD45Rbhigh T-cell transfer severe combined immunodeficiency (SCID) mouse inflammatory bowel disease model demonstrated that oral administration of STA-5326 markedly reduced inflammatory histopathologic changes in the colon. A striking decrease in interferon-γ (IFN-γ) production was observed in ex vivo culture of lamina propria cells harvested from animals treated with STA-5326, indicating a down-regulation of the Th1 response by STA-5326. These results suggest that STA-5326 has potential for use in the treatment of Th1-related autoimmune or immunologic disorders. STA-5326 currently is being evaluated in phase 2 clinical trials in patients with Crohn disease and rheumatoid arthritis.
Impaired ribosome biogenesis in Diamond-Blackfan anemia
Authors: Choesmel Valérie , Bacqueville Daniel , Rouquette Jacques , Noaillac-Depeyre Jacqueline , Fribourg Sébastien , Crétien Aurore , Leblanc Thierry , Tchernia Gil , Da Costa Lydie , Gleizes Pierre-Emmanuel 
Published: October 2006

Abstract
The gene encoding the ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia. The consequence of these mutations on the onset of the disease remains obscure. Here, we show that RPS19 plays an essential role in biogenesis of the 40S small ribosomal subunit in human cells. Knockdown of RPS19 expression by siRNAs impairs 18S rRNA synthesis and formation of 40S subunits and induces apoptosis in HeLa cells. Pre-rRNA processing is altered, which leads to an arrest in the maturation of precursors to the 18S rRNA. Under these conditions, pre-40S particles are not exported to the cytoplasm and accumulate in the nucleoplasm of the cells in perinuclear dots. Consistently, we find that ribosome biogenesis and nucleolar organization is altered in skin fibroblasts from DBA patients bearing mutations in the RPS19 gene. In addition, maturation of the 18S rRNA is also perturbed in cells from a patient bearing no RPS19-related mutation. These results support the hypothesis that DBA is directly related to a defect in ribosome biogenesis and indicate that yet to be discovered DBA-related genes may be involved in the synthesis of the ribosomal subunits.
Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals
Authors: Yoder Mervin C. , Mead Laura E. , Prater Daniel , Krier Theresa R. , Mroueh Karim N. , Li Fang , Krasich Rachel , Temm Constance J. , Prchal Josef T. , Ingram David A. 
Published: October 2006

AbstractThe limited vessel-forming capacity of infused endothelial progenitor cells (EPCs) into patients with cardiovascular dysfunction may be related to a misunderstanding of the biologic potential of the cells. EPCs are generally identified by cell surface antigen expression or counting in a commercially available kit that identifies “endothelial cell colony-forming units” (CFU-ECs). However, the origin, proliferative potential, and differentiation capacity of CFU-ECs is controversial. In contrast, other EPCs with blood vessel-forming ability, termed endothelial colony-forming cells (ECFCs), have been isolated from human peripheral blood. We compared the function of CFU-ECs and ECFCs and determined that CFU-ECs are derived from the hematopoietic system using progenitor assays, and analysis of donor cells from polycythemia vera patients harboring a Janus kinase 2 V617F mutation in hematopoietic stem cell clones. Further, CFU-ECs possess myeloid progenitor cell activity, differentiate into phagocytic macrophages, and fail to form perfused vessels in vivo. In contrast, ECFCs are clonally distinct from CFU-ECs, display robust proliferative potential, and form perfused vessels in vivo. Thus, these studies establish that CFU-ECs are not EPCs and the role of these cells in angiogenesis must be re-examined prior to further clinical trials, whereas ECFCs may serve as a potential therapy for vascular regeneration.