bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoglobulin A (IgA) Responses and IgE-Associated Inflammation along the Respiratory Tract after Mucosal but Not Systemic Immunization
Authors: Hodge Lisa M. , Marinaro Mariarosaria , Jones Harlan P. , McGhee Jerry R. , Kiyono Hiroshi , Simecka Jerry W. 
Published: July 2002

ABSTRACTThe purpose of the present study was to determine the extent of immunologic responses, particularly immunopathologic responses, within the upper and lower respiratory tracts after intranasal immunization using the mucosal adjuvant cholera toxin (CT). BALB/c mice were nasally immunized with influenza virus vaccine combined with CT. The inclusion of the mucosal adjuvant CT clearly enhanced generation of antibody responses in both the nasal passages and lungs. After nasal immunization, antigen-specific immunoglobulin A (IgA) antibody-forming cells dominated antibody responses throughout the respiratory tract. However, IgG responses were significant in lungs but not in nasal passages. Furthermore, parenteral immunization did not enhance humoral immunity in the upper respiratory tract even after a nasal challenge, whereas extrapulmonary lymphoid responses enhanced responses in the lung. After nasal immunization, inflammatory reactions, characterized by mononuclear cell infiltration, developed within the lungs of mice but not in nasal passages. Lowering dosages of CT reduced, but did not eliminate, these adverse reactions without compromising adjuvancy. Serum IgE responses were also enhanced in a dose-dependent manner by inclusion of CT. In summary, there are differences in the generation of humoral immunity between the upper respiratory tract and the lung. As the upper respiratory tract is in a separate compartment of the immune system from that stimulated by parenteral immunization, nasal immunization is an optimal approach to generate immunity throughout the respiratory tract. Despite the promise of nasal immunization, there is also the potential to develop adverse immunopathologic reactions characterized by pulmonary airway inflammation and IgE production.
Perturbation and Proinflammatory Type Activation of Vδ1+γδ T Cells in African Children withPlasmodium falciparumMalaria
Authors: Hviid Lars , Kurtzhals Jørgen A. L. , Adabayeri Victoria , Loizon Severine , Kemp Kåre , Goka Bamenla Q. , Lim Annick , Mercereau-Puijalon Odile , Akanmori Bartholomew D. , Behr Charlotte 
Published: July 2002

ABSTRACTγδ T cells have variously been implicated in the protection against, and the pathogenesis of, malaria, but few studies have examined the γδ T-cell response to malaria in African children, who suffer the large majority of malaria-associated morbidity and mortality. This is unfortunate, since available data suggest that simple extrapolation of conclusions drawn from studies of nonimmune adults ex vivo and in vitro is not always possible. Here we show that both the frequencies and the absolute numbers of γδ T cells are transiently increased following treatment ofPlasmodium falciparummalaria in Ghanaian children and they can constitute 30 to 50% of all T cells shortly after initiation of antimalarial chemotherapy. The bulk of the γδ T cells involved in this perturbation expressed Vδ1 and had a highly activated phenotype. Analysis of the T-cell receptors (TCR) of the Vδ1+cell population at the peak of their increase showed that all expressed Vγ chains were used, and CDR3 length polymorphism indicated that the expanded Vδ1 population was highly polyclonal. A very high proportion of the Vδ1+T cells produced gamma interferon, while fewer Vδ1+cells than the average proportion of all CD3+cells produced tumor necrosis factor alpha. No interleukin 10 production was detected among TCR-γδ+cells in general or Vδ1+cells in particular. Taken together, our data point to an immunoregulatory role of the expanded Vδ1+T-cell population in this group of semi-immuneP. falciparummalaria patients.
Bactericidal Activity of Human Eosinophilic Granulocytes againstEscherichia coli
Authors: Persson Terese , Andersson Pia , Bodelsson Mikael , Laurell Martin , Malm Johan , Egesten Arne 
Published: July 2002

ABSTRACTEosinophils participate in allergic inflammation and may have roles in the body's defense against helminthic infestation. Even under noninflammatory conditions, eosinophils are present in the mucosa of the large intestine, where large numbers of gram-negative bacteria reside. Therefore, roles for eosinophils in host defenses against bacterial invasion are possible. In a system for bacterial viable counts, the bactericidal activity of eosinophils and the contribution of different cellular antibacterial systems againstEscherichia coliwere investigated. Eosinophils showed a rapid and efficient killing ofE. coliunder aerobic conditions, whereas under anaerobic conditions bacterial killing decreased dramatically. In addition, diphenylene iodonium chloride (DPI), an inhibitor of the NADPH oxidase and thereby of superoxide production, also significantly inhibited bacterial killing. The inhibitor of nitric oxide (NO) productionl-N5-(1-iminoethyl)-ornithine dihydrochloride did not affect the killing efficiency, suggesting that NO or derivatives thereof are of minor importance under the experimental conditions used. To investigate the involvement of superoxide and eosinophil peroxidase (EPO) in bacterial killing, EPO was blocked by azide. The rate ofE. colikilling decreased significantly in the presence of azide, whereas addition of DPI did not further decrease the killing, suggesting that superoxide acts in conjunction with EPO. Bactericidal activity was seen in eosinophil extracts containing granule proteins, indicating that oxygen-independent killing may be of importance as well. The findings suggest that eosinophils can participate in host defense against gram-negative bacterial invasion and that oxygen-dependent killing, i.e., superoxide acting in conjunction with EPO, may be the most important bactericidal effector function of these cells.
Helicobacter hepaticus-Induced Colitis in Interleukin-10-Deficient Mice: Cytokine Requirements for the Induction and Maintenance of Intestinal Inflammation
Authors: Kullberg Marika C. , Rothfuchs Antonio Gigliotti , Jankovic Dragana , Caspar Patricia , Wynn Thomas A. , Gorelick Peter L. , Cheever Allen W. , Sher Alan 
Published: July 2002

ABSTRACTWe have previously shown that specific-pathogen-free interleukin-10 (IL-10)-deficient (IL-10 KO) mice reconstituted withHelicobacter hepaticusdevelop severe colitis associated with a Th1-type cytokine response. In the present study, we formally demonstrate that IL-12 is crucial for disease induction, because mice deficient for both IL-10 and IL-12 p40 show no intestinal pathology followingH. hepaticusinfection. By using monoclonal antibodies (MAbs) to IL-12, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), we have further analyzed the role of these cytokines in the maintenance of the Th1 response and inflammation in IL-10 KO mice with establishedH. hepaticus-induced colitis. Treatment of infected colitic IL-10 KO mice with anti-IL-12 p40 resulted in markedly reduced intestinal inflammation, colonic IFN-γ, TNF-α, and inducible nitric oxide synthase (iNOS) mRNA levels, andH. hepaticus-specific IFN-γ secretion by mesenteric lymph node (MLN) cells compared to the findings in control MAb-treated mice. Moreover, the diminished pathology was associated with decreased numbers of colonic CD3+T cells and significantly reduced frequencies ofHelicobacter-reactive CD4+Th1 cells in MLN. In contrast, anti-IFN-γ and/or anti-TNF-α had no effect on intestinal inflammation in IL-10 KO mice with established colitis. Using IL-10/IFN-γ double-deficient mice, we further show that IFN-γ is not required for the development of colitis follwingH. hepaticusinfection. MLN cells from infected IL-10/IFN-γ KO animals secreted elevated amounts of IL-12 and TNF-α following bacterial antigen stimulation, indicating alternative pathways of disease induction. Taken together, our results demonstrate a crucial role for IL-12 in both inducing and sustaining intestinal inflammation through recruitment and maintenance of a pool of pathogenic Th1 cells.
CdtA, CdtB, and CdtC Form a Tripartite Complex That Is Required for Cytolethal Distending Toxin Activity
Authors: Lara-Tejero Marı́a , Galán Jorge E. 
Published: July 2002

ABSTRACTCampylobacter jejuniencodes a cytolethal distending toxin (CDT) that causes cells to arrest in the G2/M transition phase of the cell cycle. Highly related toxins are also produced by other important bacterial pathogens. CDT activity requires the function of three genes:cdtA, cdtB, andcdtC. Recent studies have established that CdtB is the active subunit of CDT, exerting its effect as a nuclease that damages the DNA and triggers cell cycle arrest. Microinjection of CdtB into target cells led to G2/M arrest and cytoplasmic distention, in a manner indistinguishable from that caused by CDT treatment. Despite this progress, nothing is known about the composition of the CDT holotoxin or the function of CdtA and CdtC. We show here that, when applied individually, purified CdtA, CdtB, or CdtC does not exhibit toxic activity. In contrast, CdtA, CdtB, and CdtC when combined, interact with one another to form an active tripartite holotoxin that exhibits full cellular toxicity. CdtA has a domain that shares similarity with the B chain of ricin-related toxins. We therefore proposed that CDT is a tripartite toxin composed of CdtB as the enzymatically active subunit and of CdtA and CdtC as the heterodimeric B subunit required for the delivery of CdtB.
Immune Response to Chlamydial 60-Kilodalton Heat Shock Protein in Tears from Nepali Trachoma Patients
Authors: Hessel Tracey , Dhital S. P. , Plank Rebeca , Dean Deborah 
Published: July 2002

ABSTRACT

Although the host immune response to the 60-kDa chlamydial heat shock protein (hsp60) has been implicated in trachoma pathogenesis, no studies have examined mucosal immune responses to hsp60 in populations for which chlamydia is endemic. Tears and sera from Nepali villagers were reacted against hsp60 fusion proteins, whole hsp60, and the major outer membrane protein (MOMP). Tears from villagers without disease were anti-hsp60 immunoglobulin G (IgG) reactive in 6 (38%) of 16 villagers compared with 36 (90%) of 40 with follicular trachoma (TF) (
P
< 0.001); 47 (89%) of 53 with inflammatory trachoma (TI) (
P
< 0.001); and 31 (84%) of 37 with conjunctival scarring (TS) (
P
= 0.002). By multivariate analysis, odds ratios for tear hsp60 IgG immunoreactivity in villagers with TF, TI, and TS were 49.2 (confidence interval [CI], 2.7 to 898), 22.6 (CI, 3 to 170), and 13.6 (CI, 1.4 to 133), respectively. There were no significant differences for tear IgA or secretory IgA (sIgA) reactivity to hsp60 or for tear sIgA and IgG reactivity to MOMP. Serum anti-hsp60 IgG immunoreactivity was associated with TI only. These data suggest that anti-hsp60 IgG immunoreactivity represents largely locally derived antibodies, which may promote disease pathology. In contrast, nonspecific high rates of anti-hsp60 sIgA antibodies suggest chronic or repeat stimulation from an endemic source of organisms.
Dendritic Cells Can Initiate Protective Immune Responses against Malaria
Authors: Bruña-Romero Oscar , Rodriguez Ana 
Published: July 2002

ABSTRACTAn understanding of the antigen presentation mechanisms that mediate induction of protective immune responses against malaria is essential for the development of successful immunization approaches. Here we show that dendritic cells presentingPlasmodium yoeliisporozoite antigens are able to activate specific CD4+and CD8+T cells and initiate protective immune responses against malaria in mice.
Filarial Antigens Impair the Function of Human Dendritic Cells during Differentiation
Authors: Semnani Roshanak Tolouei , Sabzevari Helen , Iyer Ramesh , Nutman Thomas B. 
Published: July 2002

ABSTRACTThe antigen-specific T-cell unresponsiveness seen in lymphatic filariasis is mediated, in part, by diminished antigen-presenting cell function and is most specific for microfilariae (MF), the parasite stage found in large numbers in the peripheral circulation. We investigated the effect of MF antigen (MFAg) on dendritic cells (DC) in both their differentiation process from monocyte precursors and also after they have developed into DC. When MFAg was added to cultures of monocytes during their differentiation process to immature DC, the production of interleukin 12 (IL-12) p40, p70 protein, and IL-10 was significantly (P< 0.03) inhibited in response toStaphylococcus aureusCowan (SAC) and SAC-gamma interferon (IFN-γ) (60% to 80% inhibition). IL-10 was also inhibited (P= 0.04) in response to CD40 ligand–IFN-γ. Moreover, MFAg inhibited the mRNA expression of IL-12 p40 and IL-10 as assessed by RNA protection assays. This effect was antigen specific, as another parasite antigen (solubleToxoplasma gondiiantigen) did not inhibit the production of these cytokines. This effect was also not a result of diminished cell viability nor of an alteration in surface expression of most costimulatory surface molecules, including major histocompatibility complex class I and class II. In contrast to exposure throughout the differentiation process, MFAg added to immature DC had no effect on DC cytokine expression. Although MF-differentiated DC were capable of inducing an allogeneic mixed lymphocyte reaction, they did so to a significantly lesser degree than DC without antigen exposure. These data collectively suggest that once DC are differentiated from their precursor cells, they become resistant to changes by MFAg.
Host Defense Functions of Proteolytically Processed and Parent (Unprocessed) Cathelicidins of Rabbit Granulocytes
Authors: Zarember Kol A. , Katz Seth S. , Tack Brian F. , Doukhan Laurence , Weiss Jerrold , Elsbach Peter 
Published: July 2002

ABSTRACTMembers of the cathelicidin family are present in all mammals studied. Generally, these proteins contain a conserved N-terminal domain and a structurally and functionally divergent C-terminal region that expresses antibacterial or other activities when proteolytically released. Rabbit granulocytes produce CAP18, a cathelicidin that conforms to this structural and functional organization, and also 15-kDa protein isoforms (p15s) that share several key structural features with other cathelicidins but apparently do not undergo processing with release of an active peptide. To further define the importance of proteolysis in the antibacterial activities of these proteins, we have purified from granulocytes proCAP18, its C-terminal peptide (CAP18p), and two p15 isoforms to apparent homogeneity. Of these four polypeptides, only CAP18p was independently cytotoxic to encapsulatedEscherichia coli(90% inhibitory concentration, ∼600 nM) but it was ∼50-fold less potent on a molar basis than the bactericidal/permeability-increasing protein (BPI). However, all four cathelicidin species, notably including proCAP18, exhibited antibacterial synergy with BPI, and the p15s also displayed synergy with CAP18p in the absence of BPI. Subnanomolar concentrations of proCAP18 blocked lipopolysaccharide-induced chemiluminescence of human leukocytes, showing a molar potency more than 100-fold greater than that of CAP18p (∼20 nM) or BPI (∼50 nM). Thus, while independent bactericidal activity of cathelicidins requires processing, other host-defense functions do not and are more potently expressed by the unprocessed protein than by the C-terminal peptide.
Intracellular Survival ofLeishmania majorin Neutrophil Granulocytes after Uptake in the Absence of Heat-Labile Serum Factors
Authors: Laufs Helmut , Müller Kerstin , Fleischer Jens , Reiling Norbert , Jahnke Nicole , Jensenius Jens C. , Solbach Werner , Laskay Tamás 
Published: July 2002

ABSTRACTThe role of polymorphonuclear neutrophil granulocytes (PMN) in defense against the intracellular parasiteLeishmaniais poorly understood. In the present study, the interaction of human PMN withLeishmania majorpromastigotes was investigated in vitro. In the presence of fresh human serum, about 50% of PMN phagocytosed the parasites within 10 min and the parasite uptake led to PMN activation, resulting in the killing of most ingested parasites. Heat inactivation of the serum markedly reduced the rate of early parasite phagocytosis, suggesting a role of complement components in the early uptake ofLeishmania. However, over 50% of PMN were able to ingest parasites in the presence of heat-inactivated serum if the coincubation was extended to 3 h. After 3 h, 10% of the PMN were found to internalizeLeishmaniaeven under serum-free conditions. These findings indicate that PMN possess mechanisms for both opsonin/complement-dependent and -independent uptake ofLeishmania. Both pathways of uptake could be partially blocked by anti-CR3 antibody. Mannan-binding lectin was found not to be involved in this process. When phagocytosed in the absence of opsonin, the majority ofLeishmaniaparasites survived intracellularly in PMN for at least 1 day. These data suggest a dual role of PMN in the early response toL. majorinfection. On the one hand, PMN can rapidly eliminate the intracellular parasites, and on the other hand,Leishmaniacan survive intracellularly in PMN. These data, together with the finding that intact parasites were seen in PMN isolated from the skin of infected mice, suggest that PMN can serve as host cells for the intracellular survival ofLeishmaniawithin the first hours or days after infection.
Toxoplasma gondii-Infected Human Myeloid Dendritic Cells Induce T-Lymphocyte Dysfunction and Contact-Dependent Apoptosis
Authors: Wei Shuang , Marches Florentina , Borvak Jozef , Zou Weiping , Channon Jacqueline , White Michael , Radke Jay , Cesbron-Delauw Marie-France , Curiel Tyler J. 
Published: July 2002

ABSTRACTDendritic cells ignite adaptive immunity by priming naïve T lymphocytes. Human monocyte-derived dendritic cells (MDDCs) infected withToxoplasma gondiiinduce T-lymphocyte gamma interferon production and may thus activateT. gondii-specific immunity. However, we now demonstrate thatT. gondii-infected MDDCs are poor at activating T lymphocytes and are unable to induce specific cytotoxic T lymphocytes. On the other hand, MDDCs acquiring nonviableT. gondiiantigens directly, or indirectly through captured apoptotic or necrotic cell bodies, induce potent T-lymphocyte activation. T lymphocytes exposed to infected MDDCs are significantly impaired in upregulation of CD69 and CD28, are refractory to activation, and die through contact-dependent apoptosis mediated by an as-yet-unidentified mechanism not requiring Fas, tumor necrosis factor-related apoptosis-inducing ligand, leukocyte function antigen 1, intercellular adhesion molecule 1, tumor necrosis factor alpha, interleukin 10, alpha interferon, gamma interferon, prostaglandins, or reactive nitrogen intermediates. Bystander T lymphocytes that were neither infected nor apoptotic were refractory to activation, suggesting global dysfunction. Immunosuppression and T-lymphocyte unresponsiveness and apoptosis are typical of acuteT. gondiiinfection. Our data suggest that infected dendritic cells contribute to these processes. On the other hand, host cells infected withT. gondiiare resistant to multiple inducers of apoptosis. Thus, regulation of host cell and bystander cell apoptosis by viableT. gondiimay be significant components of a strategy to evade immunity and enhance intracellular parasite survival.
Upregulation of Thymosin β-10 byMycobacterium bovisInfection of Bovine Macrophages Is Associated with Apoptosis
Authors: Gutiérrez-Pabello José A. , McMurray David N. , Adams L. Garry 
Published: July 2002

ABSTRACTBovine macrophages underwent apoptosis as a result of infection with aMycobacterium bovisfield strain. Macrophages infected with a multiplicity of infection (MOI) of 25:1 developed chromatin condensation and DNA fragmentation at 4 h and 8 h, respectively, whereas changes in chromatin condensation induced by MOIs of 10:1 and 1:1 required more time and had a reduced number of apoptotic cells. Not only infected macrophages underwent apoptosis, but also uninfected bystander macrophages became apoptotic. Increased differential expression of thymosin β-10 was identified inM. bovis-infected bovine macrophages by differential display reverse transcriptase PCR. Phagocytosis of latex beads had no effect on the expression of thymosin β-10, whereas bacterial suspensions upregulated thymosin β-10 expression, suggesting thatM. bovisor mycobacterial products are essential in the process. Heat-inactivatedM. bovisinduced a slight increase in thymosin β-10 mRNA, whereas live virulent and attenuatedM. bovisorganisms increased the gene expression almost twofold. A mouse macrophage cell line (RAW 264.7) overexpressing the bovine thymosin β-10 transgene had spontaneous apoptosis at a higher rate (66.5%) than parental cells (4.7%) or RAW cells harboring the empty vector (22.8%). The apoptotic rates of the overexpressing cells were significantly higher when compared with both the empty vector transfected (P< 0.01) and parental cells (P< 0.001). Our evidence suggests that upregulation of thymosin β-10 inM. bovis-infected macrophages is linked with increased cell death due to apoptosis.
Functional Substitution of the TibC Protein of Enterotoxigenic
Escherichia coli
Strains for the Autotransporter Adhesin Heptosyltransferase of the AIDA System
Authors: Moormann Corinna , Benz Inga , Schmidt M. Alexander 
Published: July 2002

ABSTRACT

The plasmid-encoded AIDA (adhesin involved in diffuse adherence) autotransporter protein derived from diffuse-adhering clinical
Escherichia coli
isolate 2787 and the TibA (enterotoxigenic invasion locus B) protein encoded by the chromosomal
tib
locus of enterotoxigenic
E. coli
(ETEC) strain H10407 are posttranslationally modified by carbohydrate substituents. Analysis of the AIDA-I adhesin showed that the modification involved heptose residues. AIDA-I is modified by the heptosyltransferase activity of the product of the
aah
gene, which is located directly upstream of adhesin-encoding gene
aidA
. The carbohydrate modification of the TibA adhesin/invasin is mediated by the TibC protein but has not been elucidated. Based on the sequence similarities between TibC and AAH (autotransporter adhesin heptosyltransferase) and between the TibA and the AIDA proteins we hypothesized that the AIDA system and the Tib system encoded by the
tib
locus are structurally and functionally related. Here we show that (i) TibC proteins derived from different ETEC strains appear to be highly conserved, (ii) recombinant TibC proteins can substitute for the AAH heptosyltransferase in introducing the heptosyl modification to AIDA-I, (iii) this modification is functional in restoring the adhesive function of AIDA-I, (iv) a single amino acid substitution at position 358 completely abolishes this activity, and (v) antibodies directed at the functionally active AIDA-I recognize a protein resembling modified TibA in ETEC strains. In summary, we conclude that, like AAH, TibC represents an example of a novel class of heptosyltransferases specifically transferring heptose residues onto multiple sites of a protein backbone. A potential consensus sequence for the modification site is suggested.