bluuebunny/crossref_metadata_2025_split huggingface dataset:
T-Cell-Mediated Immune Responses in Patients with Cutaneous or Mucosal Leishmaniasis: Long-Term Evaluation after Therapy
Authors: Da-Cruz Alda Maria , Bittar Rita , Mattos Marise , Oliveira-Neto Manuel P. , Nogueira Ricardo , Pinho-Ribeiro Vanessa , Azeredo-Coutinho Rilza Beatriz , Coutinho Sergio G. 
Published: July 2002

ABSTRACTT-cell immune responses in patients with cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) were studied during the active disease, at the end of therapy, and 1 to 17 years posttherapy (long-term follow-up). Lymphocyte proliferative responses, phenotypic characterization of CD4+and CD8+Leishmania-reactive T cells, and cytokine production were assayed. Patients with active ML and CL showed higher proportions of CD4+than CD8+T cells. In CL, the healing process was associated with a decrease of CD4+and an increase of CD8+, leading to similar CD4+and CD8+proportions. This pattern was only seen in ML after long-term therapy. Long-term follow-up of patients with CL showed a positive CD4+/CD8+ratio as observed during the active disease, although the percentages of these T cell subsets were significantly lower. Patients with CL did not show significant differences between gamma interferon (IFN-γ) and interleukin-5 (IL-5) production during the period of study. Patients with active ML presented higher IFN-γ and IL-5 levels compared to patients with active CL. IL-4 was only detected during active disease. Patients long term after cure from ML showed increasing production of IFN-γ, significant decrease of IL-5, and no IL-4 production. Two apparently beneficial immunological parameters were detected in tegumentary leishmaniasis: (i) decreasing proportions of CD4+Leishmania-reactive T cells in the absence of IL-4 production associated with cure of CL and ML and (ii) decreasing levels of IL-5 long after cure, better detected in patients with ML. The observed T-cell responses maintained for a long period in healed patients could be relevant for immunoprotection against reinfection and used as a parameter for determining the prognosis of patients and selecting future vaccine preparations.
Defective Induction of Interleukin-12 in Human Monocytes by Germ-Tube Forms ofCandida albicans
Authors: Chiani Paola , Bromuro Carla , Torosantucci Antonella 
Published: July 2002

ABSTRACTYeast (Y) to germ-tube (GT) transition ofCandida albicansis considered a putative virulence trait. On the other hand, interleukin-12 (IL-12) is a key promoter of T-helper type 1 protective immunity against this human opportunistic pathogen. We studied IL-12 production by human monocytes cocultured in vitro with Y or GT forms ofC. albicans. Following stimulation by Y cells, monocytes produced appreciable levels of IL-12, which, upon addition of gamma interferon (IFN-γ), compared to those achievable by lipopolysaccharide (100 ng/ml) stimulation (140 ± 65 and 185 ± 80 pg/ml, respectively [mean ± standard deviation in four independent experiments]). In contrast, IL-12 production by GT cell-stimulated monocytes was much lower or absent (<5 pg/ml) and could not be brought to the level induced by Y cells by the addition of IFN-γ (30 ± 10 pg/ml in the four independent experiments above). Besides being observed as actual cytokine production, this lower response was also observed as specific IL-12 p40 mRNA transcript and was not associated with hyperproduction of the IL-12-competing cytokine IL-10. Phagocytosis and killing experiments in the presence of cytochalasin D showed that IL-12 production by Y cell-stimulated monocytes was phagocytosis dependent and that GT cells ofC. albicanswere not phagocytized by the human monocytes. Importantly, however, Y and GT cells were equally killed by the monocytes. Thus, the virulence trait attributed to the Y-GT transition ofC. albicansmight also be related to the lack of induction by GT cells of a protective anticandidal immunity through defective IL-12 production.
Lectin Site Interaction with Capsular Polysaccharide Mediates Nonimmune Phagocytosis of Type III Group B Streptococci
Authors: Albanyan Esam A. , Edwards Morven S. 
Published: July 2002

ABSTRACTGroup BStreptococcus(GBS) causes substantial morbidity but most individuals exposed to the organism remain healthy. These experiments tested the hypothesis that engagement of the complement receptor 3 (CR3) lectin site would effectively trigger neutrophil-mediated phagocytosis of complement-opsonized type III GBS by nonimmune human sera. Using an opsonophagocytosis assay, saccharides identified as interacting with the CR3 lectin site effectively inhibited neutrophil-mediated killing of type III, strain COH1. Fructose, which does not interact with the lectin site, promoted significantly less inhibition of opsonophagocytosis. Saccharide-mediated inhibition was reversed in a dose-related fashion by addition of type III, GBS capsular polysaccharide-specific immunoglobulin G. When capsule-deficient or asialo mutant type III strains were employed, the lectin site was not required. Structurally defined GBS serotypes with a side chain at least two sugars in length engaged the lectin site, andN-acetyld-glucosamine was not a required component monosaccharide. Intact type III capsular polysaccharide interacted significantly more efficiently with the lectin site than did oligosaccharides representing approximately 5 or 20 repeating units, respectively. Taken together, these experiments indicate that interaction of type III GBS capsular polysaccharide with the lectin site of CR3 effects phagocytosis of these organisms by nonimmune serum. Use of this mechanism of innate immunity provides a potential explanation for the infrequency with which susceptible individuals exposed to type III GBS develop invasive infection.
Genetic Vaccination against Malaria Infection by Intradermal and Epidermal Injections of a Plasmid Containing the Gene Encoding thePlasmodium bergheiCircumsporozoite Protein
Authors: Weiss Richard , Leitner Wolfgang W. , Scheiblhofer Sandra , Chen Defeng , Bernhaupt Andrea , Mostböck Sven , Thalhamer Josef , Lyon Jeffrey A. 
Published: July 2002

ABSTRACTThe circumsporozoite protein (CSP) from the surface of sporozoite stagePlasmodiumsp. malaria parasites is among the most important of the malaria vaccine candidates. Gene gun injection of genetic vaccines encodingPlasmodium bergheiCSP induces a significant protective effect against sporozoite challenge; however, intramuscular injection does not. In the present study we compared the immune responses and protective effects induced byP. bergheiCSP genetic vaccines delivered intradermally with a needle or epidermally with a gene gun. Mice were immunized three times at 4-week intervals and challenged by a single infectious mosquito bite. Although 50 times more DNA was administered by needle than by gene gun, the latter method induced significantly greater protection against infection. Intradermal injection of the CSP genetic vaccine induced a strong Th1-type immune response characterized by a dominant CSP-specific immunoglobulin G2a (IgG2a) humoral response and high levels of gamma interferon produced by splenic T cells. Gene gun injection induced a predominantly Th2-type immune response characterized by a high IgG1/IgG2a ratio and significant IgE production. Neither method generated measurable cytotoxic T lymphocyte activity. The results indicate that a gene gun-mediated CS-specific Th2-type response may be best for protecting against malarial sporozoite infection when the route of parasite entry is via mosquito bite.
Protective and Nonprotective Epitopes from Amino Termini of M Proteins from Australian Aboriginal Isolates and Reference Strains of Group A Streptococci
Authors: Brandt Evelyn R. , Teh Terrence , Relf Wendy A. , Hobb Rhonda I. , Good Michael F. 
Published: July 2002

ABSTRACTThe M protein is the primary vaccine candidate to prevent group A streptococcal (GAS) infection and the subsequent development of rheumatic fever (RF). However, the large number of serotypes have made it difficult to design a vaccine against all strains. We have taken an approach of identifying amino-terminal M protein epitopes from GAS isolates that are highly prevalent in GAS-endemic populations within the Northern Territory (NT) of Australia. Australian Aboriginals in the NT experience the highest incidence of RF worldwide. To develop a vaccine for this population, 39 peptides were synthesized, representing the amino-terminal region of the M protein from endemic GAS. Mice immunized with these peptides covalently linked to tetanus toxoid and emulsified in complete Freund's adjuvant raised high-titer antibodies. Over half of these sera reduced bacterial colony counts by >80% against the homologous isolate of GAS. Seven of the peptide antisera also cross-reacted with at least three other heterologous peptides by enzyme-linked immunosorbent assay. Antiserum to one peptide, BSA101–28, could recognize six other peptides, and five of these peptides could inhibit opsonization mediated by BSA101–28antiserum. Cross-opsonization studies showed that six of these sera could opsonize at least one heterologous isolate of GAS. These data reveal vaccine candidates specific to a GAS-endemic area and show the potential of some to cross-opsonize multiple isolates of GAS. This information will be critical when considering which epitopes may be useful in a multiepitope vaccine to prevent GAS infection.
Dual Role of Signaling Pathways Leading to Ca2+and Cyclic AMP Elevation in Host Cell Invasion byTrypanosoma cruzi
Authors: Caler Elisabet V. , Morty Rory E. , Burleigh Barbara A. , Andrews Norma W. 
Published: July 2002

ABSTRACTCell invasion by the protozoan parasiteTrypanosoma cruziinvolves activation of host signaling pathways and the recruitment and fusion of lysosomes at the parasite entry site. A major signaling pathway regulating invasion of fibroblasts, epithelial cells, and myoblasts involves mobilization of Ca2+from intracellular stores and requires the activity of aT. cruziserine peptidase, oligopeptidase B (OPB). Deletion of the OPB gene results in a marked defect in trypomastigote virulence, consistent with a greatly reduced cell invasion capacity. Here we show that uptake by macrophages, on the other hand, is largely independent of OPB expression and sensitive to inhibition of by cytochalasin D. The residual invasion capacity of OPBnull trypomastigotes in fibroblasts still involves lysosome recruitment, although in a significantly delayed fashion. Transient elevations in intracellular Ca2+concentrations were observed in host cells exposed to both wild-type and OPBnull trypomastigotes, but the signals triggered by the mutant parasites were less vigorous and delayed. The capacity of triggering elevation in host cell cyclic AMP (cAMP), however, was unaltered in OPBnull trypomastigotes. Modulation in cAMP levels preferentially affected the residual cell invasion capacity of OPBnull parasites, suggesting that this signaling pathway can play a dominant role in promoting cell invasion in the absence of the major OPB-dependent pathway.
Identification of a
Mycobacterium bovis
BCG Auxotrophic Mutant That Protects Guinea Pigs against
M. bovis
and Hematogenous Spread of
Mycobacterium tuberculosis
without Sensitization to Tuberculin
Authors: Chambers Mark A. , Williams Ann , Gavier-Widén Dolores , Whelan Adam , Hall Graham , Marsh Philip D. , Bloom Barry R. , Jacobs William R. , Hewinson R. Glyn 
Published: July 2002

ABSTRACT

Tuberculosis remains one of the most significant diseases of humans and animals. The only currently available vaccine against this disease is a live, attenuated vaccine, bacillus Calmette-Guérin (BCG), which was originally derived from
Mycobacterium bovis
and despite its variable efficacy is the most widely administered vaccine in the world. With the advent of the human immunodeficiency virus-AIDS pandemic concern has been raised over the safety of BCG. Moreover, since BCG sensitizes vaccinated individuals to the tuberculin test, vaccination with BCG prevents diagnosis of infection in vaccinated individuals. Recently, auxotrophic strains of BCG have been generated by insertional mutagenesis which have been shown to be safer than the parent BCG strain following administration to mice with severe combined immunodeficiency disease. These strains have also been shown to give comparable protection against intravenous and intratracheal challenge of BALB/c mice with
M. tuberculosis
relative to conventional BCG. Here we report that one of these mutants, a leucine auxotroph of BCG, conferred significant protection of the lungs and spleens of guinea pigs infected with
M. bovis
and protection of the spleens of guinea pigs infected with
M. tuberculosis
in the absence of a cutaneous hypersensitivity reaction to tuberculin. Therefore, protective immunity to tuberculosis may, at least in part, be achieved without sensitization to the tuberculin skin test. These results indicate that it may be possible to develop a new generation of vaccines based on BCG that are protective, are safe for use in the immunocompromised, and do not preclude the use of the tuberculin skin test in both humans and animals.
The Arginine Finger Domain of ExoT Contributes to Actin Cytoskeleton Disruption and Inhibition of Internalization ofPseudomonas aeruginosaby Epithelial Cells and Macrophages
Authors: Garrity-Ryan L. , Kazmierczak B. , Kowal R. , Comolli J. , Hauser A. , Engel J. N. 
Published: July 2002

ABSTRACTPseudomonas aeruginosa, an important nosocomial pathogen of humans, expresses a type III secretion system that is required for virulence. Previous studies demonstrated that the lung-virulent strain PA103 has the capacity to be either cytotoxic or invasive. Analyses of mutants suggest that PA103 delivers a negative regulator of invasion, or anti-internalization factor, to host cells via a type III secretion system. In this work we show that the type III secreted protein ExoT inhibits the internalization of PA103 by polarized epithelial cells (Madin-Darby canine kidney cells) and J774.1 macrophage-like cells. ExoS, which is closely related to ExoT but has additional ADP-ribosylating activity, can substitute for ExoT as an anti-internalization factor. ExoT contains a signature arginine finger domain found in GTPase-activating proteins. Mutation of the conserved arginine in ExoT diminished its anti-internalization activity and altered its ability to disrupt the actin cytoskeleton. Cell fractionation experiments showed that ExoT is translocated into host cells and that mutation of the arginine finger did not disrupt translocation. In a mouse model of acute pneumonia, PA103ΔUΔT reached the lungs as efficiently as PA103ΔU but showed reduced colonization of the liver. This finding suggests that the ability to resist internalization may be important for virulence in vivo.
Identification ofCowdria ruminantiumAntigens That Stimulate Proliferation of Lymphocytes from Cattle Immunized by Infection and Treatment or with Inactivated Organisms
Authors: Van Kleef Mirinda , Gunter Nico J. , Macmillan Henriette , Allsopp Basil A. , Shkap Varda , Brown Wendy C. 
Published: July 2002

ABSTRACTCowdria ruminantiumis an obligate intracellular pathogen that causes heartwater in ruminants. Several findings suggest that T cells play an important role in protection against the disease. In order to identify which proteins are involved in T-cell immunity,C. ruminantiumproteins were fractionated by continuous-flow electrophoresis and tested for their ability to stimulate lymphocyte proliferation in vitro.C. ruminantium-infected endothelial cell lysates were fractionated at between 11 and 38 kDa and 50 and 168 kDa on 15 and 7% acrylamide gels, respectively. In an attempt to stimulate the natural infective process, peripheral blood mononuclear cells (PBMC) were obtained from two cattle rendered immune by infection and treatment and assayed in proliferation assays with fractionated proteins. In a parallel study, four cattle were immunized with inactivatedC. ruminantiumto determine whether their lymphocytes also responded to fractionated proteins. Proliferation assays after immunization by infection and treatment detected noC. ruminantium-specific proliferation in vitro after one vaccination. Proliferation was observed, however, between 1 and 4 weeks after challenge. This was followed by a period of no detectable response, after which the response reappeared. PBMC from animals immunized with inactivated organisms proliferated specifically in response to antigen soon after the first immunization. OnlyC. ruminantiumproteins with low molecular masses of 11, 12, 14 to 17, and 19 to 23 kDa induced proliferative responses by lymphocytes from all six animals. These protein fractions may have potential as vaccine antigens.
Matrix Metalloproteinases Contribute to Brain Damage in Experimental Pneumococcal Meningitis
Authors: Leib Stephen L. , Leppert David , Clements John , Täuber Martin G. 
Published: July 2002

ABSTRACTThe present study was performed to evaluate the role of matrix metalloproteinases (MMP) in the pathogenesis of the inflammatory reaction and the development of neuronal injury in a rat model of bacterial meningitis. mRNA encoding specific MMPs (MMP-3, MMP-7, MMP-8, and MMP-9) and the inflammatory cytokine tumor necrosis factor alpha (TNF-α) were significantly (P< 0.04) upregulated, compared to the β-actin housekeeping gene, in cortical homogenates at 20 h after infection. In parallel, concentrations of MMP-9 and TNF-α in cerebrospinal fluid (CSF) were significantly increased in rats with bacterial meningitis compared to uninfected animals (P= 0.002) and showed a close correlation (r= 0.76;P< 0.001). Treatment with a hydroxamic acid-type MMP inhibitor (GM6001; 65 mg/kg intraperitoneally every 12 h) beginning at the time of infection significantly lowered the MMP-9 (P< 0.02) and TNF-α (P< 0.02) levels in CSF. Histopathology at 25.5 ± 5.7 h after infection showed neuronal injury (median [range], 3.5% [0 to 17.5%] of the cortex), which was significantly (P< 0.01) reduced to 0% (0 to 10.8%) by GM6001. This is the first report to demonstrate that MMPs contribute to the development of neuronal injury in bacterial meningitis and that inhibition of MMPs may be an effective approach to prevent brain damage as a consequence of the disease.
The Cytotoxic T-Lymphocyte Epitope of thePlasmodium falciparumCircumsporozoite Protein Also Modulates the Efficiency of Receptor-Ligand Interaction with Hepatocytes
Authors: Rathore Dharmendar , McCutchan Thomas F. 
Published: July 2002

ABSTRACTMalaria sporozoites are transmitted from the mosquito salivary gland to host hepatocytes within minutes of an infectious bite. The circumsporozoite protein (CS), which covers the surface ofPlasmodiumsporozoites, functions during these minutes in the targeting of host liver cells. The protein's potentially important role in an antimalaria vaccine has spawned interest in both the host immune responses to the parasite's presence and the actual functional role of the protein in the targeting of host liver cells. Here we show that the region of CS known to elicit a cytotoxic T-lymphocyte (CTL) response to irradiated sporozoites also, somewhat ironically, mediates the receptor-ligand interaction essential to parasite invasion of the host. Hence, the structure of CS represents a balance of potentially counterdirectional forces. Polymorphism in the CTL epitope appears to be a product of this balanced state as opposed to an “arms race” as it is so often portrayed. The conceptual difference between the theories regarding the maintainance of polymorphism in CTL epitopes may have significant implication for vaccine design.
Alkyl Hydroperoxide Reductases C and D Are Major Antigens Constitutively Expressed by
Mycobacterium avium
subsp.
paratuberculosis
Authors: Olsen Ingrid , Reitan Liv J. , Holstad Gudmund , Wiker Harald G. 
Published: July 2002

ABSTRACT

Antigens characteristic for
Mycobacterium avium
subspecies
paratuberculosis
were identified by crossed immunoelectrophoresis (CIE) and by absorbing out cross-reactive antigens by using a polyclonal and polyvalent
Mycobacterium avium
subspecies
avium
antiserum. Two antigens were present in
M. avium
subsp.
paratuberculosis
and not detected in
Mycobacterium avium
subsp.
avium
. They were identified as antigens 17 and 20 in a CIE reference system for
M. avium
subsp.
paratuberculosis
antigens. Purified antigen 20 was identified as alkyl hydroperoxide reductase C (AhpC) while the N-terminal part of purified antigen 17 showed 80% homology with alkyl hydroperoxide reductase D (AhpD) of
Mycobacterium tuberculosis
. AhpC had a nonreduced mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis corresponding to a molecular mass of 45 kDa and is probably a homodimer linked with disulfide bridges in its native form. AhpD had a mobility corresponding to 19 kDa. Monospecific rabbit antiserum against AhpC and AhpD reacted with 9 strains of
M. avium
subsp.
paratuberculosis
but not with 20 other mycobacterial strains except for a
Mycobacterium gordonae
strain, against which a weak cross-reactive band was produced. Goats experimentally infected with
M. avium
subsp.
paratuberculosis
had strong gamma interferon (IFN-γ) responses toward both AhpC and AhpD, and they also had antibodies against AhpC. The ability of AhpC and AhpD to induce IFN-γ production shows that these proteins potentially could be used in future vaccines or in diagnostic assays. These results further show that AhpC and AhpD are immunologically important proteins which are constitutively and highly expressed in
M. avium
subsp.
paratuberculosis
without the bacteria being submitted to oxidative stress and that the specificities of antigens can be a matter of different levels of protein expression in various species as well as distinct structural differences.
Allele Substitution of the Streptokinase Gene Reduces the Nephritogenic Capacity of Group A Streptococcal Strain NZ131
Authors: Nordstrand Annika , McShan W. Michael , Ferretti Joseph J. , Holm Stig E. , Norgren Mari 
Published: July 2002

ABSTRACTTo investigate the role of allelic variants of streptokinase in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), site-specific integration plasmids were constructed, which contained either the non-nephritis-associated streptokinase gene (skc5) from the group C streptococcal strainStreptococcus equisimilisH46A or the nephritis-associated streptokinase gene (ska1) from the group A streptococcal nephritogenic strain NZ131. The plasmids were introduced by electroporation and homologous recombination into the chromosome of an isogenic derivative of strain NZ131, in which the streptokinase gene had been deleted and which had thereby lost its nephritogenic capacity in a mouse model of APSGN. The introduction of a non-nephritis-associated allelic variant of streptokinase did not rescue the nephritogenic capacity of the strain. The mutant and the wild-type strains produced equivalent amounts of streptokinase. Complementation of theskadeletion derivative with the originalskaallele reconstituted the nephritogenicity of wild-type NZ131. The findings support the hypothesis that the role of streptokinase in the pathogenesis of APSGN is related to the allelic variant of the protein.