bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-Dose Mucosal Immunization with Biodegradable Microparticles Containing aSchistosoma mansoniAntigen
Authors: Baras Benoît , Benoit Marie-Ange , Dupré Loïc , Poulain-Godefroy Odile , Schacht Anne-Marie , Capron André , Gillard Jean , Riveau Gilles 
Published: December 2019

ABSTRACTThe purpose of this work was to assess the immunogenicity of a single nasal or oral administration of recombinant 28-kDa glutathioneS-transferase ofSchistosoma mansoni(rSm28GST) entrapped by poly(lactide-co-glycolide) (PLG)- or polycaprolactone (PCL)-biodegradable microparticles. Whatever the polymer and the route of administration used, the equivalent of 100 μg of entrapped rSm28GST induced a long-lasting and stable antigen-specific serum antibody response, with a peak at 9 to 10 weeks following immunization. Isotype profiles were comparable, with immunoglobulin G1 being the predominant isotype produced. The abilities of specific antisera to neutralize the rSm28GST enzymatic activity have been used as criteria of immune response quality. Pooled 10-week sera from mice receiving PLG microparticles by the nasal or oral route neutralized the rSm28GST enzymatic activity, whereas sera of mice receiving either PCL microparticles, free rSm28GST, or empty microparticles inefficiently neutralized this enzymatic activity. Finally, this study shows that a single administration of these microparticles could provide distinct and timely release pulses of microencapsulated antigen, which might greatly facilitate future vaccine development.
Mechanisms of Internalization ofStaphylococcus aureusby Cultured Human Osteoblasts
Authors: Jevon Marc , Guo Chuanbin , Ma Beechai , Mordan Nicky , Nair Sean P. , Harris Malcolm , Henderson Brian , Bentley George , Meghji Sajeda 
Published: December 2019

ABSTRACTStaphylococcus aureusis an important bone pathogen, and evidence shows that this organism is internalized by chick osteoblasts. Here we report thatS. aureusis internalized by human osteoblasts. Internalization was inhibited by monodansylcadaverine and cytochalasin D and to a lesser extent by ouabain, monensin, colchicine, and nocodazole. We propose that internalization occurs via a receptor-mediated pathway, requiring the participation of cytoskeletal elements, principally actin.
Identification and Characterization of a Novel Fibronectin-Binding Protein on the Surface of Group A Streptococci
Authors: Rocha Claudia L. , Fischetti Vincent A. 
Published: December 2019

ABSTRACT

Understanding the role surface proteins play in the interaction of group A streptococci with epithelial cells is an important step toward the development of new strategies to fight infections. Fibronectin-binding proteins in streptococci and staphylococci have been described as important mediators for adherence to eukaryotic cells. In the present study we describe a new
Streptococcus pyogenes
fibronectin-binding protein (PFBP). The gene encoding the PFBP protein (
pfbp
) was identified from an M12 strain genomic library. It encodes a protein of 127.4 kDa which contains the LPXTGX motif characteristic of cell wall-associated proteins in gram-positive organisms and is among the largest surface molecules described for group A streptococci. The
pfbp
gene is transcribed during cell growth and was present in several class I and II streptococcal strains tested. The deduced amino acid sequence of PFBP exhibits a variable N-terminal region and a conserved C-terminal region when compared to most fibronectin-binding proteins identified from other gram-positive bacteria. The N-terminal region presents a stretch of 105 amino acids with no homology with N-terminal regions of previously described fibronectin-binding molecules, while the C-terminal region contains three repeat domains that share significant similarity with the repeat regions of fibronectin-binding proteins from
S. pyogenes
,
S. dysgalactiae
, and
S. equisimilis
. The PFBP repeated region, when expressed on the surface of
S. gordonii
, a commensal organism, binds to soluble and immobilized fibronectin. This study also shows that, in addition to
pfbp
, a second gene homologous with that of protein F1 (which also codes for a fibronectin-binding protein) is transcribed during cell growth in the same
S. pyogenes
strain.
Infection-Associated Decline of Cape Buffalo Blood Catalase Augments Serum Trypanocidal Activity
Authors: Wang Qin , Murphy Noel , Black Samuel J. 
Published: December 2019

ABSTRACT

Clearance of trypanosomes from the blood of infected Cape buffalo was associated with the development of two responses: (i) complement-dependent and clone-specific lytic activity and (ii) complement-independent trypanocidal activity that was not restricted by trypanosome clone or species. This latter activity was mediated by H
2
O
2
and required the presence of xanthine oxidase in serum but not the addition of purine substrates. Expression of the xanthine oxidase-dependent trypanocidal activity in Cape buffalo serum was coincident with, and required, a decline in its H
2
O
2
catabolic activity. The H
2
O
2
catabolic activity of Cape buffalo serum was due solely to catalase and declined by eightfold around the time that trypanosomes were cleared from the blood, accompanied by a fivefold drop in erythrocyte-associated catalase activity. The Cape buffalo did not develop subsequent parasitemic waves. Clearance of parasitemia in similarly infected cattle was also associated with development of trypanosome clone-specific lytic activity, but not with the acquisition of H
2
O
2
-dependent trypanocidal activity in serum, and the cattle supported recurring parasitemia. The lack of trypanocidal activity in pre- and postinfection cattle sera was due to their low content of xanthine oxidase and sustained catalase activity. These data strongly suggest that an infection-induced serum oxidative response, the efficacy of which is amplified by a decline in blood catalase, contributes to suppression of recurring parasitemia in Cape buffalo.
CD4
+
T Cells and the Proinflammatory Cytokines Gamma Interferon and Interleukin-6 Contribute to Alveolar Bone Loss in Mice
Authors: Baker Pamela J. , Dixon Mark , Evans R. Todd , Dufour Lisa , Johnson Ellis , Roopenian Derry C. 
Published: December 2019

ABSTRACT

In this study, we used a mouse model to examine the role of the adaptive immune response in alveolar bone loss induced by oral infection with the human gram-negative anaerobic bacterium
Porphyromonas gingivalis
. Severe combined immunodeficient mice, which lack B and T lymphocytes, exhibited considerably less bone loss than did immunocompetent mice after oral infection, suggesting that lymphocytes contribute to this process. Bone loss after oral infection was decreased in mice deficient in major histocompatibility complex (MHC) class II-responsive CD4
+
T cells, but no change in bone loss was observed in mice deficient in MHC class I-responsive CD8
+
T cells or NK1
+
T cells. Mice lacking the cytokine gamma interferon or interleukin-6 also demonstrated decreased bone loss. These results suggest that the adaptive immune response, and in particular CD4
+
T cells and the proinflammatory cytokines that they secrete, are important effectors of bone loss consequent to
P. gingivalis
oral infection. The studies also reinforce the utility of the mouse oral infection model in dissecting the pathobiology of periodontal disease.
Antigenic and Molecular Conservation of the Gonococcal NspA Protein
Authors: Plante Martin , Cadieux Nathalie , Rioux Clément R. , Hamel Josée , Brodeur Bernard R. , Martin Denis 
Published: December 2019

ABSTRACT

A low-molecular-weight protein named NspA (neisserial surface protein A) was recently identified in the outer membrane of all
Neisseria meningitidis
strains tested. Antibodies directed against this protein were shown to protect mice against an experimental meningococcal infection. Hybridization experiments clearly demonstrated that the
nspA
gene was also present in the genomes of the 15
Neisseria gonorrhoeae
strains tested. Cloning and sequencing of the
nspA
gene of
N. gonorrhoeae
B2 revealed an open reading frame of 525 nucleotides coding for a polypeptide of 174 amino acid residues, with a calculated molecular weight of 18,316 and a pI of 10.21. Comparison of the predicted amino acid sequence of the NspA polypeptides from the gonococcal strains B2 and FA1090, together with that of the meningococcal strain 608B, revealed an identity of 93%, suggesting that the NspA protein is highly conserved among pathogenic
Neisseria
strains. The level of identity rose to 98% when only the two gonococcal predicted NspA polypeptides were compared. To evaluate the level of antigenic conservation of the gonococcal NspA protein, monoclonal antibodies (MAbs) were generated. Four of the seven NspA-specific MAbs described in this report recognized their corresponding epitope in 100% of the 51
N. gonorrhoeae
strains tested. Radioimmunobinding assays clearly indicated that the gonococcal NspA protein is exposed at the surface of intact cells.
Differential Induction of Colitis and Gastritis in HLA-B27 Transgenic Rats Selectively Colonized withBacteroides vulgatusorEscherichia coli
Authors: Rath Heiko C. , Wilson Kenneth H. , Sartor R. Balfour 
Published: December 2019

ABSTRACTResident bacteria play an important role in initiating and perpetuating gastrointestinal inflammation. We previously demonstrated that six commensal bacteria includingBacteroides vulgatuscaused more aggressive colitis and gastritis in HLA-B27 transgenic rats than did the other five bacteria withoutB. vulgatus. This study compared the degree of gastrointestinal inflammation in gnotobiotic HLA-B27 transgenic rats monoassociated with eitherB. vulgatusorEscherichia coli. Gnotobiotic transgenic rats raised in Trexler isolators were selectively colonized with eitherB. vulgatusorE. coli. Control rats were either germfree or colonized with six common commensal bacteria (Streptococcus faecium,E. coli,Streptococcus avium,Eubacterium contortum,Peptostreptococcus productus, andB. vulgatus[DESEP-B]). After 1 month, all the rats were killed and tissues were prepared for histologic and biochemical evaluation. Colitis induced byB. vulgatusmonoassociation was almost equal to that in DESEP-B-colonized rats and was significantly more severe thanE. coli-induced colitis, which was absent by histological testing and mild by colonic myeloperoxidase and interleukin-1β concentration determinations. However, gastritis was detectable only in DESEP-B-associated rats. These studies suggest that not all resident bacteria have equal proinflammatory capabilities, sinceB. vulgatusalone is more active thanE. colialone in inducing colitis, and that colitis and gastritis result from different luminal bacterial stimuli.
Anthrax Toxin Entry into Polarized Epithelial Cells
Authors: Beauregard Kathryn E. , Wimer-Mackin Susan , Collier R. John , Lencer Wayne I. 
Published: December 2019

ABSTRACT

We examined the entry of anthrax edema toxin (EdTx) into polarized human T84 epithelial cells using cyclic AMP-regulated Cl
−
secretion as an index of toxin entry. EdTx is a binary A/B toxin which self assembles at the cell surface from anthrax edema factor and protective antigen (PA). PA binds to cell surface receptors and delivers EF, an adenylate cyclase, to the cytosol. EdTx elicited a strong Cl
−
secretory response when it was applied to the basolateral surface of T84 cells but no response when it was applied to the apical surface. PA alone had no effect when it was applied to either surface. T84 cells exposed basolaterally bound at least 30-fold-more PA than did T84 cells exposed apically, indicating that the PA receptor is largely or completely restricted to the basolateral membrane of these cells. The PA receptor did not fractionate with detergent-insoluble caveola-like membranes as cholera toxin receptors do. These findings have implications regarding the nature of the PA receptor and confirm the view that EdTx and CT coopt fundamentally different subcellular systems to enter the cell and cause disease.
Interleukin-12 Enhances Antifungal Activity of Human Mononuclear Phagocytes againstAspergillus fumigatus: Implications for a Gamma Interferon-Independent Pathway
Authors: Roilides Emmanuel , Tsaparidou Sevasti , Kadiltsoglou Isaac , Sein Tin , Walsh Thomas J. 
Published: December 2019

ABSTRACTThe potential of recombinant human interleukin-12 (IL-12) to enhance the capacity of human monocytes (MNC) to elicit an oxidative burst and damage hyphae ofAspergillus fumigatuswas investigated. Incubation of peripheral blood mononuclear cells (PBMC) from healthy adults with 10 to 100 ng of IL-12/ml at 37°C for 2 to 3 days enhanced the production of superoxide anion (O2−) in response to phorbol myristate acetate (PMA) (P= 0.04) and unopsonizedA. fumigatushyphae (P= 0.03) and further enhanced hyphal damage (P= 0.009). Anti-gamma interferon (anti-IFN-γ) blocked secretion of IFN-γ by IL-12-treated PBMC but did not inhibit IL-12-induced O2−production by these cells in response to PMA. In addition, IL-12-treated elutriated MNC secreted no IFN-γ or tumor necrosis factor alpha but exhibited enhanced O2−production compared to controls (P= 0.013). These findings demonstrate that IL-12 augments oxidative antifungal activities of MNC via an IFN-γ-independent route, suggesting a novel pathway of IL-12 action in antifungal defense.
Levels of Gamma Interferon and Interleukin-4 Are Inversely Related to the Levels of Their Corresponding Autoantibodies in Patients with Lower Respiratory Tract Infection
Authors: ElKarim Rihab , Granert Carl , Lindquist Lars , Link Hans , Bakhiet Moiz 
Published: December 2019

ABSTRACTTo study the involvement of cytokines and their corresponding autoantibodies (Aabs) in inflammatory mechanisms in patients with lower respiratory tract infections, blood samples were taken from patients at the time of admission to the hospital and before treatment. Cell-released capturing enzyme-linked immunosorbent assay was used to measure the levels of gamma interferon (IFN-γ) and interleukin-4 (IL-4) produced spontaneously by peripheral mononuclear cells (PMNC). ELISA was used to measure Aabs to these cytokines in sera. The levels of both cytokines were inversely related to the levels of their corresponding Aabs. While a high level of IFN-γ was observed together with a low level of anti-IFN-γ Aab, decreased IL-4 levels were observed with increased levels of Aabs to IL-4. Immunoglobulins were purified, digested to obtain Fab fragments, and tested for specificity and cross-reactivity. The Aabs and their Fab fragments were tested in cytokine biological assays and showed neutralizing effects. Our data demonstrated increased levels of the proinflammatory cytokine IFN-γ and decreased release of the anti-inflammatory cytokine IL-4 during early presentation of lower respiratory tract infection. The levels of these cytokines were inversely related to the levels of their corresponding Aabs that exhibited regulatory effects on the cytokine biological function in vitro.
Host Defense againstMycobacterium aviumDoes Not Have an Absolute Requirement for Major Histocompatibility Complex Class I-Restricted T Cells
Authors: Bermudez Luiz E. , Petrofsky Mary 
Published: December 2019

ABSTRACTThe role of CD8+T cells was evaluated in a mouse model of disseminatedMycobacterium aviuminfection. C57BL/6J and C57BL/6Jβ2−/−(β2−/−) mice were infected intravenously, and the number of viable bacteria in each liver and spleen was determined. No significant difference between the number of bacteria in the two strains of mice was observed at 2, 4, 6, and 8 weeks after infection. Histopathological examination of granulomas from C57BL/6J and β2−/−mice did not show any difference either in the number of organisms per granuloma or in the size of the granulomas. Investigation of the cytokine profile in the spleen demonstrated that the β2−/−strain of mice produced a significantly lower amount of gamma interferon at 8 weeks after infection and significantly increased concentrations of tumor necrosis factor alpha compared with that from the wild-type mouse. Interleukin-12 and transforming growth factor β1levels did not differ between the two strains of mice at 2, 4, 6, and 8 weeks. Although previous work had found that host response againstMycobacterium tuberculosisinvolves major histocompatibility complex class I-restricted T cells, our results indicate that chronic deficiency of CD8+T cells does not lead to a different expression of the disease and that if CD8+T cells are involved in the host response, their function can be assumed by other immune cells.
A Conventional Beagle Dog Model for Acute and Chronic Infection withHelicobacter pylori
Authors: Rossi Giacomo , Rossi Michela , Vitali Claudia G. , Fortuna Damiano , Burroni Daniela , Pancotto Laura , Capecchi Sonia , Sozzi Sabrina , Renzoni Giacomo , Braca Giovanni , Del Giudice Giuseppe , Rappuoli Rino , Ghiara Paolo , Taccini Ennio 
Published: December 2019

ABSTRACTHelicobacter pylorihas been widely recognized as an important human pathogen responsible for chronic gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Little is known about the natural history of this infection since patients are usually recognized as having the infection only after years or decades of chronic disease. Several animal models ofH. pyloriinfection, including those with different species of rodents, nonhuman primates, and germ-free animals, have been developed. Here we describe a new animal model in which the clinical, pathological, microbiological, and immunological aspects of human acute and chronic infection are mimicked and which allows us to monitor these aspects of infection within the same individuals. Conventional Beagle dogs were infected orally with a mouse-adapted strain ofH. pyloriand monitored for up to 24 weeks. Acute infection caused vomiting and diarrhea. The acute phase was followed by polymorphonuclear cell infiltration, interleukin 8 induction, mononuclear cell recruitment, and the appearance of a specific antibody response againstH. pylori. The chronic phase was characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of the typical macroscopic follicles that in humans are considered possible precursors of MALT lymphoma. In conclusion, infection in this model mimics closely human infection and allows us to study those phases that cannot be studied in humans. This new model can be a unique tool for learning more about the disease and for developing strategies for treatment and prevention.
Increase in Gamma Interferon-Secreting CD8+, as Well as CD4+, T Cells in Lungs following Aerosol Infection withMycobacterium tuberculosis
Authors: Feng Carl G. , Bean Andrew G. D. , Hooi Helena , Briscoe Helen , Britton Warwick J. 
Published: December 2019

ABSTRACTAlthough it is well established that CD4+T cells are required for the protective immune response against tuberculosis (TB), there is some evidence that CD8+T cells are also involved in the host response toMycobacterium tuberculosis. There is, however, a paucity of information on the pulmonary CD8+T-cell response during infection. We therefore have compared the changes in both CD8+and CD4+T cells following aerosol infection withM. tuberculosis. There was an observed delay between the peak of infection and the activated T-cell response in the lung. The kinetics of CD8+and CD4+T-cell responses in the lung were identical, both peaking at week 8, 4 weeks later than the peak of cellular response in draining lymph nodes. Similar changes in activation/memory phenotypes occurred on the pulmonary CD8+and CD4+T cells. Following in vitro restimulation, both subsets synthesized gamma interferon, a cytokine essential for controllingM. tuberculosisinfection. Since lung CD8+T cells are actively expanded during aerosolM. tuberculosisinfection, it is important that both CD8+and CD4+T cells be targeted in the design of future TB vaccines.
Carrageenan Primes Leukocytes To Enhance Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Production
Authors: Ogata Masanori , Matsui Takashi , Kita Toshiro , Shigematsu Akio 
Published: December 2019

ABSTRACTWe have previously reported that pretreatment with carrageenan (CAR) enhances lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α) production in and lethality for mice. Whole blood cultured in vitro was used to show that CAR pretreatment results in about a 200-fold increase in LPS-induced TNF-α production. CAR by itself did not induce TNF-α production. However, CAR-treated cultured medium sensitized whole blood to make more LPS-induced TNF than did saline-treated cultured medium in vitro. It was also demonstrated that CAR pretreatment increases TNF-α mRNA levels of both blood cells and peritoneal exudate cells, but not of bone marrow cells. Immunoelectron microscopic analysis revealed that polymorphonuclear leukocytes and macrophages are TNF-α-producing cells in CAR-treated mice. In CAR-treated mice, TNF-α was seen early after LPS injection in leukocytes in hepatic sinusoids and on the surfaces of endothelial cells. TNF-α was also detected late after LPS injection in hepatocytes which become edematous. These results suggest that CAR primes leukocytes to produce TNF-α in response to LPS and that they play an important role in the pathogenesis of liver injury.
Differences in the Carboxy-Terminal (Putative Phospholipid Binding) Domains of
Clostridium perfringens
and
Clostridium bifermentans
Phospholipases C Influence the Hemolytic and Lethal Properties of These Enzymes
Authors: Jepson Marie , Howells Angela , Bullifent Helen L. , Bolgiano Barbara , Crane Dennis , Miller Julie , Holley Jane , Jayasekera Pramukh , Titball Richard W. 
Published: December 2019

ABSTRACT

The phospholipases C of
C. perfringens
(alpha-toxin) and
C. bifermentans
(Cbp) show >50% amino acid homology but differ in their hemolytic and toxic properties. We report here the purification and characterisation of alpha-toxin and Cbp. The phospholipase C activity of alpha-toxin and Cbp was similar when tested with phosphatidylcholine in egg yolk or in liposomes. However, the hemolytic activity of alpha-toxin was more than 100-fold that of Cbp. To investigate whether differences in the carboxy-terminal domains of these proteins were responsible for differences in the hemolytic and toxic properties, a hybrid protein (N
bi
C
α
) was constructed comprising the N domain of Cbp and the C domain of alpha-toxin. The hemolytic activity of N
bi
C
α
was 10-fold that of Cbp, and the hybrid enzyme was toxic. These results confirm that the C-terminal domain of these proteins confers different properties on the enzymatically active N-terminal domain of these proteins.