bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlates of Immune Protection in Chickens Vaccinated with
Mycoplasma gallisepticum
Strain GT5 following Challenge with Pathogenic
M. gallisepticum
Strain R
low
Authors: Javed Mohammed A. , Frasca Salvatore , Rood Debra , Cecchini Katharine , Gladd Martha , Geary Steven J. , Silbart Lawrence K. 
Published: August 2005

ABSTRACT

Colonization of the avian respiratory tract with
Mycoplasma gallisepticum
results in a profound inflammatory response in the trachea, air sacs, conjunctiva, and lungs. A live attenuated
M. gallisepticum
vaccine strain, GT5, was previously shown to be protective in chickens upon challenge; however, the mechanisms by which this vaccine and others confer protection remain largely unknown. The current study evaluated several potential correlates of GT5 vaccine-mediated immune protection following challenge with the pathogenic
M. gallisepticum
strain R
low
. GT5-vaccinated chickens developed mild tracheal lesions, consisting of few and scattered, discrete, lymphofollicular aggregates in the lamina propria. In addition, low numbers of aggregated B, CD4
+
, and CD8
+
cells were observed to infiltrate the trachea, in stark contrast to the large numbers infiltrating the tracheas of sham-vaccinated chickens challenged with R
low
. Lymphofollicular aggregates were rarely observed prior to day 12 postchallenge in sham-vaccinated chickens. Instead, they contained an increasingly more cellular inflammatory response characterized by expansion of the lamina propria by lymphoplasmacytic and histiocytic infiltrates. This was due in part to expansion of interfollicular zones by large numbers of infiltrating CD4
+
and CD8
+
cells and a sizeable population of immunoglobulin A (IgA)- and IgG-secreting plasma cells. GT5-vaccinated chickens also had higher serum IgG concentrations, and significantly higher numbers of
M. gallisepticum
-specific IgG- and IgA-secreting plasma/B cells within the trachea, than did sham-vaccinated chickens. These responses were observed as early as day 4 postchallenge, indicating the importance of antibody-mediated clearance of mycoplasma in GT5-vaccinated chickens.
Involvement of Toll-Like Receptor 2 in Experimental Invasive Pulmonary Aspergillosis
Authors: Balloy Viviane , Si-Tahar Mustapha , Takeuchi Osamu , Philippe Bruno , Nahori Marie-Anne , Tanguy Myriam , Huerre Michel , Akira Shizuo , Latgé Jean-Paul , Chignard Michel 
Published: August 2005

ABSTRACTAspergillus fumigatus, an opportunistic fungal pathogen, causes severe and usually fatal invasive pulmonary aspergillosis in immunocompromised hosts. Interestingly,Drosophilacells lacking the Toll protein are prone toA. fumigatusinfection. In the current study, we looked for the involvement of Toll-like receptor 2 (TLR2) in the recognition ofA. fumigatusby analyzing the in vivo and ex vivo responses of immunocompromised TLR2−/−and TLR2+/+mice to this fungus. Upon intratracheal administration of conidia, survival and tumor necrosis factor alpha (TNF-α), interleukin-12, and macrophage inhibitory protein-2 alpha concentrations in the airspaces of TLR2−/−mice were significantly lower than those of TLR2+/+animals. In vitro analysis of TNF-α production by conidia-challenged alveolar macrophages from TLR2−/−revealed a significant deficiency in comparison with macrophages from TLR2+/+mice. Infected TLR2−/−mice also have a higher respiratory distress and a higher pathogen burden than TLR2+/+mice. These data demonstrate that TLR2 plays a significant role in the defense of the host againstA. fumigatusinfection.
Postgenomic Approach To Identify Novel
Mycobacterium leprae
Antigens with Potential To Improve Immunodiagnosis of Infection
Authors: Geluk Annemieke , Klein Michèl R. , Franken Kees L. M. C. , van Meijgaarden Krista E. , Wieles Brigitte , Pereira Kelly Cristina , Bührer-Sékula Samira , Klatser Paul R. , Brennan Patrick J. , Spencer John S. , Williams Diana L. , Pessolani Maria C. V. , Sampaio Elizabeth P. , Ottenhoff Tom H. M. 
Published: August 2005

ABSTRACT

Early detection of
Mycobacterium leprae
infection is considered an important component of strategies aiming at reducing transmission of infection, but currently available diagnostic tools often lack sufficient sensitivity and specificity to reach this goal. Recent comparative genomics have revealed the presence of 165
M. leprae
genes with no homologue in
M. tuberculosis
. We selected 17 of these genes for further study. All 17 genes were found to be expressed at the mRNA level in
M. leprae
from infected mice and from a multibacillary leprosy patient. Additional comparative genomic analyses of all currently available mycobacterial genome databases confirmed 12 candidate genes to be unique to
M. leprae
, whereas 5 genes had homologues in mycobacteria other than
M. tuberculosis
. Evaluation of the immunogenicity of all 17 recombinant proteins in PBMC from 127 Brazilians showed that five antigens (ML0576, ML1989, ML1990, ML2283, and ML2567) induced significant gamma interferon levels in paucibacillary leprosy patients, reactional leprosy patients, and exposed healthy controls but not in most multibacillary leprosy patients, tuberculosis patients, or endemic controls. Importantly, among exposed healthy controls 71% had no detectable immunoglobulin M antibodies to the
M. leprae
-specific PGL-I but responded to one or more
M. leprae
antigen(s). Collectively, the
M. leprae
proteins identified are expressed at the transcriptome level and can efficiently activate T cells of
M. leprae
-exposed individuals. These proteins may provide new tools to develop tests for specific diagnosis of
M. leprae
infection and may enhance our understanding of leprosy and its transmission.
Early Cytokine Production Is Associated with Protection from Murine Cerebral Malaria
Authors: Mitchell Andrew J. , Hansen Anna M. , Hee Leia , Ball Helen J. , Potter Sarah M. , Walker John C. , Hunt Nicholas H. 
Published: August 2005

ABSTRACTCerebral malaria (CM) is an infrequent but serious complication ofPlasmodium falciparuminfection in humans. Animal and human studies suggest that the pathogenesis of CM is immune mediated, but the precise mechanisms leading to cerebral pathology are unclear. In mice, infection withPlasmodium bergheiANKA results in CM on day 6 postinoculation (p.i.), while infection with the closely related strainP. bergheiK173 does not result in CM. Infection withP. bergheiK173 was associated with increased plasma gamma interferon (IFN-γ) at 24 h p.i. and with increased splenic and hepatic mRNAs for a range of cytokines (IFN-γ, interleukin-10 [IL-10], and IL-12) as well as the immunoregulatory enzyme indoleamine 2,3-dioxygenase. In contrast,P. bergheiANKA infection was associated with an absence of cytokine production at 24 h p.i. but a surge of IFN-γ production at 3 to 4 days p.i. When mice were coinfected with both ANKA and K173, they produced an early cytokine response, including a burst of IFN-γ at 24 h p.i., in a manner similar to animals infected withP. bergheiK173 alone. These coinfected mice failed to develop CM. In addition, in a low-doseP. bergheiK173 infection model, protection from CM was associated with early production of IFN-γ. Early IFN-γ production was present in NK-cell-depleted, γδ-cell-depleted, and Jα281−/−(NKT-cell-deficient) mice but absent from β2-microglobulin mice that had been infected withP. bergheiK173. Taken together, the results suggest that the absence of a regulatory pathway involving IFN-γ and CD8+T cells inP. bergheiANKA infection allows the development of cerebral immunopathology.
vpaH
, a Gene Encoding a Novel Histone-Like Nucleoid Structure-Like Protein That Was Possibly Horizontally Acquired, Regulates the Biogenesis of Lateral Flagella in
trh
-Positive
Vibrio parahaemolyticus
TH3996
Authors: Park Kwon-Sam , Arita Michiko , Iida Tetsuya , Honda Takeshi 
Published: August 2005

ABSTRACT

A histone-like nucleoid structure (H-NS) is a major component of the bacterial nucleoid and plays a crucial role in the global gene regulation of enteric bacteria. Here, we cloned and characterized the gene for the H-NS-like protein VpaH in
Vibrio parahaemolyticus. vpaH
encodes a protein of 134 amino acids that shows approximately 55%, 54%, and 41% identities with VicH in
Vibrio cholerae
, H-NS in
V. parahaemolyticus
, and H-NS in
Escherichia coli
, respectively. The
vpaH
gene was found in only
trh
-positive
V. parahaemolyticus
strains and not in Kanagawa-positive or in
trh
-negative environmental strains. Moreover, the G+C content of the
vpaH
gene was 38.6%, which is lower than the average G+C content of the whole genome of this bacterium (45.4%). These data suggest that
vpaH
was transmitted to
trh
-possessing
V. parahaemolyticus
strains by lateral transfer. The
vpaH
gene was located about 2.6 kb downstream of the
trh
gene, in the convergent direction of the
trh
transcription. An in-frame deletion mutant of
vpaH
lacked motility on semisolid motility assay plates. Western blot analysis and electron microscopy observations revealed that the mutant was deficient in lateral flagella biogenesis, whereas there was no defect in the expression of polar flagella. Additionally, the
vpaH
mutant showed a decreased adherence to HeLa cells and a decrease in biofilm formation compared with the wild-type strain. Introduction of the
vpaH
gene in the
vpaH
-negative strain increased the expression of lateral flagella compared with the wild-type strain. In conclusion, our findings suggest that VpaH affects lateral flagellum biogenesis in
trh
-positive
V. parahaemolyticus
strain TH3996.
Cationic Liposomes Containing Mycobacterial Lipids: a New Powerful Th1 Adjuvant System
Authors: Rosenkrands Ida , Agger Else Marie , Olsen Anja W. , Korsholm Karen S. , Andersen Claire Swetman , Jensen Klaus T. , Andersen Peter 
Published: August 2005

ABSTRACT

The immunostimulation provided by the mycobacterial cell wall has been exploited for many decades, e.g., in Freund's complete adjuvant. Recently, the underlying mechanism behind this adjuvant activity, including Toll receptor signaling, has begun to be unraveled, confirming the potential of mycobacterial constituents to act as adjuvants. In this study, the immunostimulatory properties of a
Mycobacterium bovis
BCG lipid extract were tested for their adjuvant activity. Administration of the lipids in dimethyl dioctadecyl ammonium bromide-based cationic liposomes induced a powerful Th1 response characterized by markedly elevated antigen-specific immunoglobulin G2a (IgG2a) isotype antibodies and substantial production of gamma interferon. The adjuvant formulation (designated mycosomes) elicited high levels of gamma interferon both in C57BL/6 as well as in Th2-prone BALB/c mice. Furthermore, the mycosomes induced immune responses to protein antigens from several sources including
Mycobacterium tuberculosis
,
Chlamydia muridarum
, and tetanus toxoid. In a tuberculosis challenge model, the mycosomes combined with the Ag85B-ESAT-6 fusion protein were demonstrated to have a unique ability to maintain sustained immunological memory at a level superior to live BCG.
Novel Role of the Lipopolysaccharide O1 Side Chain in Ferric Siderophore Transport and Virulence of
Vibrio anguillarum
Authors: Welch Timothy J. , Crosa Jorge H. 
Published: August 2005

ABSTRACT

From a library of approximately 20,000 transposon mutants, we have identified mutants affected in chromosomal genes involved in synthesis of the siderophore anguibactin, as well as in ferric anguibactin utilization. Genetic and sequence analyses of one such transport-defective mutant revealed that the transposon insertion occurred in an open reading frame (ORF) with homology to
rmlC
, a dTDP-rhamnose biosynthetic gene. This ORF resides within a cluster of four ORFs, all of which are predicted to function in the biosynthesis of this O side chain precursor. The same phenotype was seen in a mutant obtained by allelic exchange in
rmlD
, another ORF in this dTDP-rhamnose biosynthetic cluster. This mutation could be complemented with the wild-type
rmlD
gene, restoring both production of the O1 antigen side chain and ferric anguibactin transport. Presence of the O1 side chain was crucial for the resistance of
Vibrio anguillarum
to the bactericidal action of nonimmune serum from the fish host. Surprisingly, further analysis demonstrated that these mutations were pleiotropic, leading to a dramatic decrease in the levels of FatA, the outer membrane protein receptor for ferric anguibactin transport, and a concomitant reduction in iron transport. Thus, our results in this work demonstrate that the lipopolysaccharide O1 side chain is required for the operation of two critical virulence factors in
V. anguillarum
: serum resistance and anguibactin-mediated iron transport. These factors allow
V. anguillarum
to survive in serum and multiply in the iron-limiting milieu of the host vertebrate.
Cyclic Diguanylate Regulates
Vibrio cholerae
Virulence Gene Expression
Authors: Tischler Anna D. , Camilli Andrew 
Published: August 2005

ABSTRACT

The cyclic dinucleotide second messenger cyclic diguanylate (c-diGMP) has been implicated in regulation of cell surface properties in several bacterial species, including
Vibrio cholerae
. Expression of genes required for
V. cholerae
biofilm formation is activated by an increased intracellular c-diGMP concentration. The response regulator VieA, which contains a domain responsible for degradation of c-diGMP, is required to maintain a low concentration of c-diGMP and repress biofilm formation. The VieSAB three-component signal transduction system was, however, originally identified as a regulator of
ctxAB
, the genes encoding cholera toxin (CT). Here we show that the c-diGMP phosphodiesterase activity of VieA is required to enhance CT production. This regulation occurred at the transcriptional level, and ectopically altering the c-diGMP concentration by expression of diguanylate cyclase or phosphodiesterase enzymes also affected
ctxAB
transcription. The c-diGMP phosphodiesterase activity of VieA was also required for maximal transcription
toxT
but did not influence the activity of ToxR or expression of TcpP. Finally, a single amino acid substitution in VieA that increases the intracellular c-diGMP concentration led to attenuation in the infant mouse model of cholera. Since virulence genes including
toxT
and
ctxA
are repressed by a high concentration of c-diGMP, while biofilm genes are activated, we suggest that c-diGMP signaling is important for the transition of
V. cholerae
from the environment to the host.
Highly Immunogenic and Protective Recombinant Vaccine Candidate Expressed in Transgenic Plants
Authors: Chargelegue Daniel , Drake Pascal M. W. , Obregon Patricia , Prada Alessandra , Fairweather Neil , Ma Julian K-C. 
Published: August 2005

ABSTRACTVaccine development has been hampered by difficulties in developing new and safe adjuvants, so alternative technologies that offer new avenues forward are urgently needed. The goal of this study was to express a monoclonal recombinant immune complex in a transgenic plant. A recombinant protein consisting of a tetanus toxin C fragment-specific monoclonal antibody fused with the tetanus toxin C fragment was designed and expressed. Immune complex formation occurred between individual fusion proteins to form immune complex-like aggregates that bound C1q and FcγRIIa receptor and could be targeted to antigen-presenting cells. Unlike antigen alone, the recombinant immune fusion complexes were highly immunogenic in mice and did not require coadministration of an adjuvant (when injected subcutaneously). Indeed, these complexes elicited antibody titers that were more than 10,000 times higher than those observed in animals immunized with the antigen alone. Furthermore, animals immunized with only 1 μg of recombinant immune complex without adjuvant were fully protected against lethal challenge. This the first report on the use of a genetic fusion between antigen and antibody to ensure an optimal expression ratio between the two moieties and to obtain fully functional recombinant immune complexes as a new vaccine model.
Merozoite Surface Protein 1 of
Plasmodium vivax
Induces a Protective Response against
Plasmodium cynomolgi
Challenge in Rhesus Monkeys
Authors: Dutta Sheetij , Kaushal Deep C. , Ware Lisa A. , Puri Sunil K. , Kaushal Nuzhat A. , Narula Atul , Upadhyaya D. S. , Lanar David E. 
Published: August 2005

ABSTRACT

The 42-kDa fragment of the merozoite surface protein 1 (MSP-1
42
) is a leading candidate for the development of a vaccine to control malaria. We previously reported a method for the production of
Plasmodium vivax
MSP-1
42
(PvMSP-1
42
) as a soluble protein (S. Dutta, L. W. Ware, A. Barbosa, C. F. Ockenhouse, and D. E. Lanar, Infect. Immun.
69:
5464-5470, 2001). We report here a process to manufacture the same PvMSP-1
42
protein but as an insoluble inclusion body-derived protein which was then refolded in vitro. We compared the immunogenicity and protective efficacy of the soluble and refolded forms of PvMSP-1
42
protein by using a heterologous but closely related
P. cynomolgi
-rhesus monkey challenge model. As comparative controls we also expressed, purified, and immunized rhesus with the soluble and refolded forms of the
P. cynomolgi
MSP-1
42
(PcMSP-1
42
) proteins. All proteins induced equally high-titer, cross-reacting antibodies. Upon challenge with
P. cynomolgi
, none of the MSP-1
42
-vaccinated groups demonstrated sterile protection or a delay in the prepatent period. However, following an initial rise in parasitemia, all MSP-1-vaccinated animals had significantly lower parasite burdens as indicated by lower cumulative parasitemia, lower peak parasitemia, lower secondary peak parasitemia, and lower average daily parasitemia compared to the adjuvant control group (
P
< 0.05). Except the soluble PcMSP-1
42
group, monkeys in all other groups had fewer numbers of days with parasitemia of >10,000 parasites mm
−3
. Interestingly, there was no significant difference in the level of partial protection observed in the homologous and heterologous groups in this challenge model. The soluble and refolded forms of PcMSP-1
42
and PvMSP-1
42
proteins also appeared to have a similar partially protective effect.
Interaction of Enteropathogenic and Shiga Toxin-Producing
Escherichia coli
and Porcine Intestinal Mucosa: Role of Intimin and Tir in Adherence
Authors: Girard Francis , Batisson Isabelle , Frankel Gad M. , Harel Josée , Fairbrother John M. 
Published: August 2005

ABSTRACT

The ileal in vitro organ culture (IVOC) model using tissues originating from colostrum-deprived newborn piglets has proven to be an effective way to study the attaching and effacing (A/E) phenotype of porcine enteropathogenic
Escherichia coli
(EPEC) ex vivo. The aim of this study was to investigate the role of intimin subtype and Tir in the adherence of EPEC and Shiga-toxin-producing
E. coli
(STEC), isolated from different animal species, to porcine intestinal IVOC. Moreover, the role of intimin in Tir-independent adherence of the human EPEC strain E2348/69 was investigated using intimin and Tir-deficient derivatives. Our results demonstrated that A/E
E. coli
strains (AEEC) from various animal species and humans induce the A/E phenotype in porcine ileal IVOC and that intimin subtype influences intestinal adherence and tropism of AEEC strains. We also showed that a
tir
mutant of EPEC strain E2348/69 demonstrates close adherence to the epithelial cells of porcine ileal IVOC segments, with microvillous effacement but with no evidence of actin polymerization or pedestal formation, and that intimin seems to be involved in this phenotype. Overall, this study provides further evidence for the existence of one or more host-cell-encoded intimin receptor(s) in the pig gut.
Hydrophilic Domain II of
Escherichia coli
Dr Fimbriae Facilitates Cell Invasion
Authors: Das Margaret , Hart-Van Tassell Audrey , Urvil Petri T. , Lea Susan , Pettigrew David , Anderson K. L. , Samet Alfred , Kur Jozef , Matthews Steve , Nowicki Stella , Popov Vsevolod , Goluszko Pawel , Nowicki Bogdan J. 
Published: August 2005

ABSTRACT

Uropathogenic and diarrheal
Escherichia coli
strains expressing adhesins of the Dr family bind to decay-accelerating factor, invade epithelial cells, preferentially infect children and pregnant women, and may be associated with chronic or recurrent infections. Thus far, no fimbrial domain(s) that facilitates cell invasion has been identified. We used alanine scanning mutagenesis to replace selected amino acids in hydrophilic domain II of the structural fimbrial subunit DraE and evaluated recombinant mutant DraE for attachment, invasion, and intracellular compartmentalization. The mutation of amino acids V28, T31, G33, Q34, T36, and P40 of DraE reduced or abolished HeLa cell invasion but did not affect attachment. Electron micrographs showed a stepwise entry and fusion of vacuoles containing
Escherichia coli
mutants T36A and Q34A or corresponding beads with lysosomes, whereas vacuoles with wild-type Dr adhesin showed no fusion. Mutants T31A and Q34A, which were deficient in invasion, appeared to display a reduced capacity for clustering decay-accelerating factor. Our findings suggest that hydrophilic domain II may be involved in cell entry. These data are consistent with the interpretation that in HeLa cells the binding and invasion phenotypes of Dr fimbriae may be separated.
Paneth Cells and Antibacterial Host Defense in Neonatal Small Intestine
Authors: Sherman Michael P. , Bennett Stephen H. , Hwang Freda F. Y. , Sherman Jan , Bevins Charles L. 
Published: August 2005

ABSTRACT

Paneth cells are specialized epithelia in the small bowel that secrete antimicrobial proteins. Paneth cells are vital to the innate immunity of the small bowel in adult mammals, but their role during neonatal infection of the small bowel is not well established. Dithizone selectively damages Paneth cells, and when dithizone-treated newborn rats are infected enterally with
Escherichia coli
, the numbers of
E. coli
cells in their jejunal and ileal lavage fluid are significantly increased compared to controls. The data support that Paneth cells are necessary for neonatal antibacterial defense.
Mannheimia
(
Pasteurella
)
haemolytica
Leukotoxin Binding Domain Lies within Amino Acids 1 to 291 of Bovine CD18
Authors: Gopinath R. S. , Ambagala T. C. , Deshpande M. S. , Donis R. O. , Srikumaran S. 
Published: August 2005

ABSTRACT

Previously, we identified bovine CD18 as the receptor for leukotoxin secreted by
Mannheimia
(
Pasteurella
)
haemolytica
. In this study, we constructed bovine-murine CD18 chimeras to locate the leukotoxin binding domain on CD18. Leukotoxin specifically lysed transfectants expressing bovine CD18 fragment encompassing amino acids 1 to 291, indicating that leukotoxin binding domain lies within amino acids 1 to 291 of bovine CD18.