Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 31
Filter
1.
Clin Exp Immunol ; 203(2): 230-243, 2021 02.
Article in English | MEDLINE | ID: mdl-33080067

ABSTRACT

Galectin-10 is involved in the T cell suppressive activity of regulatory T cells and eosinophils alike. We have identified a subpopulation of T cell suppressive eosinophils that express CD16 on the surface and contain more galectin-10 compared with conventional CD16-negative eosinophils. Our main goal was to determine how the intracellular protein galectin-10 is released from eosinophils when exposed to proliferating T cells and if such release could be inhibited. Confocal microscopy and imaging flow cytometry were used to study the release of galectin-10 from eosinophils incubated with polyclonally activated T cells. T cell proliferation was monitored by measurement of the incorporation of [3 H]-thymidine. Initially, galectin-10-containing synapses formed between eosinophils and T cells. Subsequently, the plasma membrane of eosinophils began to disintegrate and cap-like accumulations of galectin-10 budded on the eosinophil cell surface. Lastly, eosinophil extracellular traps composed of nuclear DNA and galectin-10 were freed. It was solely the CD16-expressing suppressive eosinophils that formed synapses and eosinophil extracellular traps containing galectin-10. Dissolution of the extracellular traps by DNase I partly abrogated the T cell suppression exerted by eosinophils. Extracellular trap formation has mainly been associated with anti-bacterial defense, but we show a new putative function of these cellular formations, as mediators of T cell suppression by enabling the release of galectin-10 from eosinophils.


Subject(s)
Cell Proliferation/physiology , Eosinophils/metabolism , Galectins/metabolism , T-Lymphocytes, Regulatory/metabolism , Cells, Cultured , Eosinophils/immunology , Extracellular Traps/immunology , Extracellular Traps/metabolism , Galectins/immunology , Humans , Kinetics , Leukocyte Count/methods , Leukocytes, Mononuclear , Lymphocyte Activation/immunology , Receptors, IgG/immunology , Receptors, IgG/metabolism , T-Lymphocytes, Regulatory/immunology
2.
Ticks Tick Borne Dis ; 8(5): 715-720, 2017 08.
Article in English | MEDLINE | ID: mdl-28539197

ABSTRACT

The most common tick-borne human disease in Norway is Lyme borreliosis. Ticks in Norway also harbour less known disease-causing agents such as Candidatus Neoehrlichia mikurensis, Borrelia miyamotoi and Rickettsia helvetica. However, human infections caused by these pathogens have never been described in Norway. The main aims of the study were to evaluate the contribution of several tick-borne bacterial agents, other than Borrelia burgdorferi sensu lato, to zoonotic diseases in Norway and to determine their clinical pictures. Blood samples from 70 symptomatic tick-bitten adults from the Agder counties in southern Norway were screened for seven tick-borne pathogens by using a commercial multiplex PCR-based method and by singleplex real-time PCR protocols. Most patients (65/70) presented with a rash clinically diagnosed as erythema migrans (EM). The most frequently detected pathogen DNA was from Ca. N. mikurensis and was found in the blood of 10% (7/70) of the patients. The Ca. N. mikurensis-infected patients presented with an EM-like rash as the only symptom. B. burgdorferi s.l. DNA was present in the blood of 4% (3/70) of the study participants. None had detectable Anaplasma phagocytophilum, B. miyamotoi, Rickettsia typhus group or spotted fever group, Francisella tularensis, Coxiella burnetii or Bartonella spp. DNA in the blood. The commercially available multiplex PCR bacteria flow chip system failed to identify half of the infected patients detected by corresponding real-time PCR protocols. The recovery of Ca. N. mikurensis DNA was higher in the pellet/plasma fraction of blood than from whole blood. To conclude, Ca. N. mikurensis appeared to be the etiological agent in patients with EM in a surprisingly large fraction of tick-bitten persons in the southern part of Norway.


Subject(s)
Anaplasmataceae Infections/epidemiology , Anaplasmataceae/isolation & purification , Borrelia burgdorferi Group/isolation & purification , Erythema Chronicum Migrans/epidemiology , Adult , Aged , Anaplasmataceae/genetics , Anaplasmataceae Infections/blood , Anaplasmataceae Infections/microbiology , Borrelia burgdorferi Group/classification , Borrelia burgdorferi Group/genetics , Erythema Chronicum Migrans/blood , Erythema Chronicum Migrans/microbiology , Female , Humans , Male , Middle Aged , Norway/epidemiology , Prevalence , RNA, Bacterial/genetics , RNA, Ribosomal/genetics , Sequence Analysis, DNA , Seroepidemiologic Studies , Young Adult
3.
Allergy ; 72(9): 1406-1414, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28194801

ABSTRACT

BACKGROUND: Eosinophilic esophagitis (EoE) afflicts both children and adults. It has been debated whether pediatric EoE and adult EoE represent different disease entities. The objectives of this study were to determine whether the blood eosinophil molecular pattern of children with EoE is (i) distinct from that of healthy children; and (ii) different from that of adults with EoE. METHODS: Blood eosinophils from children and adults with EoE, and healthy controls, were analyzed with flow cytometry regarding levels of CD23, CD44, CD54, CRTH2, FOXP3, and galectin-10. Eosinophil FOXP3 and galectin-10 mRNA levels were determined by qPCR. The data were analyzed using a multivariate method of pattern recognition. RESULTS: An eosinophil molecular pattern capable of distinguishing children with EoE from control children was identified. A smaller fraction of eosinophils from children with EoE expressed CD44 and a larger fraction expressed CRTH2 than the controls. Eosinophils from children with EoE also had higher levels of galectin-10 mRNA and lower levels of FOXP3 mRNA. The eosinophils from children with EoE had lower levels of surface CD54 and of FOXP3 mRNA compared with the eosinophils from the adult patients. A key finding was the detection in healthy individuals of age-related differences in the levels of several eosinophil markers. CONCLUSIONS: Children with EoE can be distinguished from healthy children based on the molecular patterns of their blood eosinophils. Age-related physiologic differences in eosinophil molecular patterns may partly explain the different blood eosinophil phenotypes in children vs adults with EoE.


Subject(s)
Biomarkers/blood , Eosinophilic Esophagitis/diagnosis , Eosinophils/chemistry , Adolescent , Adult , Age Factors , Aged , Case-Control Studies , Child , Child, Preschool , Eosinophilic Esophagitis/blood , Female , Flow Cytometry , Humans , Male , Middle Aged , RNA, Messenger/analysis , Young Adult
4.
Clin Exp Immunol ; 187(3): 455-465, 2017 03.
Article in English | MEDLINE | ID: mdl-27921303

ABSTRACT

Eosinophilic esophagitis (EoE) is an antigen-driven T cell-mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin-10 and have T cell suppressive capacity similar to regulatory T cells (Tregs ). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell-driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction. In addition, eosinophilic expression of forkhead box protein 3 (FOXP3), the canonical transcription factor of Tregs , was determined by conventional and imaging flow cytometry, quantitative polymerase chain reaction (qPCR), confocal microscopy and immunoblotting. It was found that blood eosinophils from EoE patients had T cell suppressive capacity, and that a fraction of the eosinophils expressed FOXP3. A comparison of EoE eosinophils with healthy control eosinophils indicated that the patients' eosinophils had inferior suppressive capacity. Furthermore, a higher percentage of the EoE eosinophils expressed FOXP3 protein compared with the healthy eosinophils, and they also had higher FOXP3 protein and mRNA levels. FOXP3 was found in the cytosol and nucleus of the eosinophils from both the patients and healthy individuals, contrasting with the strict nuclear localization of FOXP3 in Tregs . To conclude, these findings suggest that the immunoregulatory function of eosinophils may be impaired in EoE.


Subject(s)
Eosinophilic Esophagitis/immunology , Eosinophils/immunology , Forkhead Transcription Factors/immunology , T-Lymphocytes, Regulatory/immunology , Adolescent , Adult , Aged , Female , Humans , Inflammation/immunology , Leukocyte Count/methods , Male , Middle Aged , Young Adult
5.
Transplant Proc ; 48(1): 185-90, 2016.
Article in English | MEDLINE | ID: mdl-26915866

ABSTRACT

BACKGROUND: Graft-versus-host disease (GVHD) that develops after intestinal or multivisceral transplantation is difficult to diagnose and is associated with high morbidity and mortality. MATERIAL AND METHODS: The objectives of this study were to investigate the incidence, clinical picture, risk factors, and outcome of GVHD in a Scandinavian cohort of patients who underwent intestinal or multivisceral transplantation during a period of 16 years (1998-2014). All transplanted patients (n = 26) were retrospectively analyzed with respect to donor- and recipient-derived risk factors. The diagnosis of GVHD was based on clinical signs, chimerism analyses of leukocytes, and histopathologic findings in biopsy specimens. RESULTS: Five of 26 patients (19%) were diagnosed with GVHD, of which three had skin GVHD, one had skin and bone marrow GVHD, and one had passenger leukocyte syndrome. Only multivisceral-transplanted patients developed GVHD. Risk factors for development of GVHD were an underlying tumor diagnosis and neoadjuvant chemo- or brachytherapy administered before intestinal transplantation. All patients were given high-dose corticosteroids as first line treatment for their GVHD, and all survived their episodes of GVHD. CONCLUSIONS: The risk of GVHD appears to be increased in recipients of multivisceral transplantations who received chemotherapy due to an underlying malignancy. The reasons may be the large amount of lymphoid tissue in these types of grafts, and the cytotoxic effects of the malignancy and chemotherapy on healthy recipient tissues. These patients should be monitored closely for the development of GVHD.


Subject(s)
Graft vs Host Disease/etiology , Intestines/transplantation , Viscera/transplantation , Adult , Aged , Female , Graft vs Host Disease/diagnosis , Graft vs Host Disease/epidemiology , Humans , Incidence , Leukocytes/immunology , Male , Middle Aged , Retrospective Studies , Risk Factors , Sweden/epidemiology , Tissue Donors , Transplantation Chimera , Transplantation, Homologous/adverse effects
6.
Clin Microbiol Infect ; 21(7): 621-30, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25770773

ABSTRACT

Candidatus Neoehrlichia mikurensis, which has rodents as its natural hosts, is an emerging tick-borne pathogen in Europe and Asia. This intracellular bacterium causes the infectious disease neoehrlichiosis. Immunocompromised patients may contract a severe form of neoehrlichiosis with high fever and vascular/thromboembolic events. As it is not detected with routine culture-based methods, neoehrlichiosis is underdiagnosed.


Subject(s)
Anaplasmataceae Infections/epidemiology , Anaplasmataceae Infections/transmission , Anaplasmataceae/isolation & purification , Tick-Borne Diseases/epidemiology , Tick-Borne Diseases/transmission , Anaplasmataceae Infections/pathology , Animals , Arthropod Vectors , Asia/epidemiology , Disease Reservoirs , Europe/epidemiology , Humans , Immunocompromised Host , Rodentia , Tick-Borne Diseases/pathology , Ticks
7.
Eur J Clin Microbiol Infect Dis ; 34(5): 917-25, 2015 May.
Article in English | MEDLINE | ID: mdl-25573536

ABSTRACT

Detection of the fungal cell wall component beta-glucan (BG) in serum is increasingly used to diagnose invasive fungal infections (IFI), but its optimal use in hematology patients with high risk of IFI is not well defined. We retrospectively analyzed the diagnostic accuracy, optimal cut-off level, and potential confounding factors of BG reactivity. The inclusion criteria were: adult patients with hematologic disease who were admitted to the hematology ward during the 2-year study period and who had two or more consecutive BG assays performed. In total, 127 patients were enrolled. Thirteen patients with proven or probable IFI, as defined by the 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, were identified. Receiver operating characteristic (ROC) curve analysis showed a high overall diagnostic performance (area under the ROC curve = 0.98) and suggested an optimal cut-off level of 158 pg/ml, with a sensitivity and a specificity of 92 % and 96 %, respectively. Multiway analysis of variance indicated that treatment with pegylated asparaginase (p < 0.001), admission to the intensive care unit (ICU; p = 0.0007), and treatment with albumin, plasma, or coagulation factors (p = 0.01) are potential confounding factors of BG reactivity. We propose that a higher cut-off level than that recommended by the manufacturer should be used to monitor adult hematology patients at high risk for IFI. Our results also suggest that elevated BG levels in patients treated with pegylated asparaginase, albumin, plasma, or coagulation factors, or those admitted to the ICU should be interpreted with caution.


Subject(s)
Diagnostic Tests, Routine/methods , Hematologic Diseases/complications , Mycoses/diagnosis , Serum/chemistry , beta-Glucans/blood , Adolescent , Adult , Aged , Data Interpretation, Statistical , False Positive Reactions , Female , Humans , Male , Middle Aged , ROC Curve , Retrospective Studies , Sensitivity and Specificity , Young Adult
8.
Clin Microbiol Infect ; 15(7): 680-3, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19624509

ABSTRACT

The present study aimed to improve the rate of detection of blood-borne microbes by using PCRs with pan-bacterial and Candida specificity. Seventeen per cent of the blood samples (n=178) collected from 107 febrile patients with haematological malignancies were positive using standard culture (BacT/Alert system). Candida PCR was positive in 12 patients, only one of whom scored culture-positive. Bacterial PCR using fresh blood samples was often negative, but the detection rate increased when the blood was pre-incubated for 2 days. These data indicate that PCR assays might be a complement for the detection of blood-borne opportunists in immunocompromised haematology patients.


Subject(s)
Bacteremia , Blood/microbiology , Candida/isolation & purification , Fungemia , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/isolation & purification , Hematologic Neoplasms/complications , Polymerase Chain Reaction/methods , Bacteremia/epidemiology , Bacteremia/microbiology , Candida/classification , Candida/genetics , Candida albicans/genetics , Candida albicans/isolation & purification , Candida glabrata/genetics , Candida glabrata/isolation & purification , Candidiasis/microbiology , Culture Media , DNA, Bacterial/analysis , DNA, Fungal/analysis , Fever , Fungemia/epidemiology , Fungemia/microbiology , Gram-Negative Bacteria/genetics , Gram-Positive Bacteria/genetics , Humans , Immunocompromised Host , Neutropenia , Opportunistic Infections/epidemiology , Opportunistic Infections/microbiology
9.
Scand J Immunol ; 67(4): 377-84, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18282233

ABSTRACT

It has been reported that extracts from common aeroallergens directly activate eosinophils from non-allergic individuals, eliciting chemotaxis and degranulation. The aims of this study were to compare the reactivity of eosinophils from non-atopic and atopic individuals to airborne allergens, and to assess if this reactivity was modulated by natural exposure to birch pollen. Blood-derived eosinophils were stimulated with allergen extracts from birch pollen, cat dander, house dust mite and timothy grass, and their capacity to degranulate (eosinophil peroxidase, EPO; major basic protein, MBP) and produce T helper type 1 and 2 cytokines were evaluated as well as their capacity to migrate in vitro, in and out of the birch pollen season. Eosinophils from atopic and non-atopic individuals responded similarly to stimulation with allergen extracts with respect to directed migration, EPO and MBP release, which was independent of the season when the samples were collected. Interestingly, eosinophils from both study groups were incapable of producing tumour necrosis factor-alpha (TNF-alpha) during the birch pollen season, but could generate interleukin-4. Innate responsiveness of eosinophils to aeroallergens is independent of the atopic status of the individual. In vivo exposure to birch allergen as seen during the birch pollen season downregulates the capacity of eosinophils to produce the cytokine TNF-alpha.


Subject(s)
Allergens/immunology , Environmental Illness/immunology , Eosinophils/immunology , Adult , Aged , Allergens/adverse effects , Animals , Antigens, Dermatophagoides/immunology , Betula/adverse effects , Betula/immunology , Cells, Cultured , Cytokines/biosynthesis , Eosinophil Peroxidase/metabolism , Eosinophils/metabolism , Female , Humans , Interleukin-4/biosynthesis , Male , Middle Aged , Mites/immunology , Myelin Basic Protein , Nerve Tissue Proteins/metabolism , Plant Extracts/immunology , Pollen/adverse effects , Transcription Factors/metabolism , Tumor Necrosis Factor-alpha/biosynthesis
10.
Biochem Pharmacol ; 74(7): 1050-6, 2007 Oct 01.
Article in English | MEDLINE | ID: mdl-17692291

ABSTRACT

The anti-inflammatory drug piroxicam has been reported to affect the production of reactive oxygen species in phagocytes. This anti-inflammatory effect is thought to be mediated through inhibition of cyclooxygenase (COX), an enzyme important for prostaglandin synthesis. We have compared the effects of piroxicam on superoxide production mediated by two closely related G-protein coupled receptors expressed on neutrophils, the formyl peptide receptor (FPR) and the formyl peptide receptor like 1 (FPRL1). Neutrophils were stimulated with agonists that bind specifically to FPR (the peptide ligand N-formyl-Met-Leu-Phe, fMLF) or FPRL1 (the peptide ligand Trp-Lys-Tyr-Met-Val-L-Met-NH(2), WKYMVM) or both of these receptors (the peptide ligand Trp-Lys-Tyr-Met-Val-D-Met-NH(2), WKYMVm). Piroxicam reduced the neutrophil superoxide production induced by the FPR agonist but had no significant effect on the FPRL1 induced response. Neutrophil intracellular calcium changes induced by the agonist WKYMVm (that triggers both FPR and FPRL1) were only inhibited by piroxicam when the drug was combined with the FPRL1 specific antagonist, Trp-Arg-Trp-Trp-Trp-Trp (WRW(4)), and this was true also for the inhibition of superoxide anion release. Receptor-binding analysis showed that the fluorescently labelled FPR specific ligand N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys (fNLFNYK), was competed for in a dose-dependent manner, by the FPR ligand fMLF and as well as by piroxicam. We show that piroxicam inhibits the neutrophil responses triggered through FPR, but not through FPRL1 and this inhibition is due to a reduced binding of the activating ligand to its cell surface receptor.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Neutrophils/drug effects , Piroxicam/pharmacology , Receptors, Formyl Peptide/metabolism , Receptors, Lipoxin/metabolism , Dose-Response Relationship, Drug , Humans , Ligands , Oligopeptides/pharmacology , Protein Binding/drug effects , Receptors, Formyl Peptide/agonists , Receptors, Formyl Peptide/antagonists & inhibitors , Receptors, Lipoxin/antagonists & inhibitors , Superoxides/metabolism
11.
J Endotoxin Res ; 7(6): 442-6, 2001.
Article in English | MEDLINE | ID: mdl-11753214

ABSTRACT

Shigella infections lead to severe inflammation associated with destruction of colonic mucosa. We assessed the effect of in vivo blockade of CD14 on the outcome of experimental Shigella infection in rabbits. A total of 17 rabbits were divided into two groups: 8 received a single i.v. dose of anti-rabbit CD14 monoclonal antibody prior to infection with an invasive Shigella flexneri strain; the remainder served as controls. The anti-CD14-treated rabbits exhibited more severe tissue destruction and a 50-fold increase in bacterial invasion of the intestinal mucosa when compared to controls. Similar numbers of polymorphonuclear leukocytes were recruited to the intestinal mucosa in both groups despite the massive bacterial invasion seen in the CD14-blocked group. No statistically significant differences were seen in levels of IL-1beta nor in the ratio of IL-1RA/IL-1beta for either group. In contrast, higher quantities of TNF-alpha were observed in the CD14-blocked group. To conclude, anti-CD14 treatment had a detrimental effect on the capacity of Shigella-infected animals to clear the infection.


Subject(s)
Antibodies, Blocking/pharmacology , Antibodies, Monoclonal/pharmacology , Dysentery, Bacillary/immunology , Lipopolysaccharide Receptors/physiology , Shigella flexneri/pathogenicity , Animals , Cell Degranulation , Colon/pathology , Cytokines/analysis , Dysentery, Bacillary/microbiology , Dysentery, Bacillary/pathology , Humans , Immunohistochemistry , Interleukin-1/analysis , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Lipopolysaccharide Receptors/immunology , Macrophages/immunology , Mutation , Rabbits , Shigella flexneri/genetics , Shigella flexneri/immunology , Shigella flexneri/isolation & purification , Tumor Necrosis Factor-alpha/analysis
13.
Infect Immun ; 68(10): 6077-81, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10992527

ABSTRACT

Cholera toxin (CT)-specific antibody responses of the immunoglobulin E (IgE) isotype in the sera of adult patients suffering from infection with either Vibrio cholerae O1, V. cholerae O139, or enterotoxigenic Escherichia coli (ETEC) were analyzed and compared with those in the sera of volunteers immunized with a bivalent B subunit O1/O139 whole-cell cholera vaccine. A significant IgE response to CT was observed in 90% of the patients with V. cholerae O1 infection (18 of 20; P = <0.001) and 95% of the patients with V. cholerae O139 infection (19 of 20; P = <0.001). Similarly, the majority of the patients with ETEC diarrhea (83%; 13 of 15) showed a positive IgE response to CT. Eight of 10 North American volunteers (80%) orally challenged with V. cholerae O1 showed CT-specific IgE responses (P = 0.004). In contrast, Swedish volunteers immunized with the oral cholera vaccine showed no IgE responses to CT (P value not significant). During the study period, total IgE levels in the sera of the diarrheal patients, the North American volunteers, and the Swedish cholera vaccinees alike remained unchanged. However, the total IgE levels in the sera of patients and healthy Bangladeshi controls were on average 89-fold higher than those in the sera of the healthy Swedish volunteers and 34-fold higher than those in the sera of the North American volunteers.


Subject(s)
Cholera Vaccines/administration & dosage , Cholera/immunology , Enterotoxins/immunology , Escherichia coli Infections/immunology , Immunoglobulin E/blood , Adolescent , Adult , Antibodies, Bacterial/blood , Cholera/microbiology , Escherichia coli/immunology , Escherichia coli/metabolism , Humans , Male , Middle Aged , Vaccination , Vibrio cholerae/immunology
14.
Vaccine ; 18(24): 2704-12, 2000 Jun 01.
Article in English | MEDLINE | ID: mdl-10781858

ABSTRACT

We have compared the B cell responses evoked in Bangladeshi, adults (n=11, median age 25 years) and children (n=21, median age 4.5 years), 7 days after intake of each of two doses of an oral, inactivated enterotoxigenic Escherichia coli (ETEC) vaccine composed of formalin-killed ETEC strains expressing the colonization factors, CFA/I, CFA/II and CFA/IV together with 1 mg of recombinant cholera toxin B-subunit (rCTB). The vaccine was well tolerated and only gave rise to negligible side effects. Peak antibody-secreting cell (ASC) response of the IgA isotype were seen 7 days after the first dose of the vaccine. The ASC responses to the different colonization factors (CFs) increased from a 29- to 46-fold (responder frequency 90-100%) in the adults and 13- to 24-fold (responder frequency 67-90%) in the children. The IgA-ASC response to rCTB also peaked after the first dose in the adults (426-fold, responder frequency 100%) and the children (46-fold, responder frequency 95%). Increased IgA antibody levels against CFA/I as well as IgA and IgG antibody levels to rCTB were seen in plasma after immunisation. About 86% of the children and 80% of the adults responded with faecal antibodies to rCTB, whereas about 67% of both groups responded to CFA/I. These results show that a single dose of the ETEC vaccine may elicit significant mucosal immune responses in both children and adults residing in an ETEC-endemic country such as Bangladesh.


Subject(s)
Bacterial Vaccines/immunology , Cholera Toxin/immunology , Cholera Vaccines/immunology , Escherichia coli/immunology , Adult , Antibodies, Bacterial/biosynthesis , Bangladesh , Child , Child, Preschool , Drug Evaluation , Enterotoxins , Female , Humans , Immunoglobulin A/biosynthesis , Male , Vaccines, Conjugate/immunology
15.
J Immunol ; 164(6): 3214-21, 2000 Mar 15.
Article in English | MEDLINE | ID: mdl-10706713

ABSTRACT

Shigella is a diarrheal pathogen that causes disease through invasion of the large intestinal mucosa. The endotoxin of the invading bacterium may play a key role in the disease process by causing inflammation and tissue injury during infection. Earlier studies have shown that various animal species lacking functional CD14 were protected against endotoxin-mediated shock. Rabbits experimentally infected with Shigella were used to test the hypothesis that blockade of endotoxin-induced cell activation with anti-CD14 mAb would diminish inflammation and thus disease severity. Unexpectedly, we observed that the intestinal mucosa of anti-CD14-treated animals exhibited a 50-fold increase in bacterial invasion and more severe tissue injury compared with controls. Despite higher bacterial loads in treated animals, the numbers of polymorphonuclear leukocytes that were recruited to the infection site were similar to those in controls. Furthermore, the phagocytic cells of CD14-blocked animals produced IL-1 and TNF-alpha. Moreover, in vitro blockade of CD14 did not impede bactericidal activity. Thus, anti-CD14 treatment interfered with host defense mechanisms involved with removal/eradication of Shigella.


Subject(s)
Antibodies, Blocking/pharmacology , Antibodies, Monoclonal/pharmacology , Dysentery, Bacillary/immunology , Dysentery, Bacillary/pathology , Lipopolysaccharide Receptors/immunology , Shigella flexneri/pathogenicity , Animals , Cell Degranulation/immunology , Cell Movement/immunology , Cytokines/biosynthesis , Dysentery, Bacillary/microbiology , Intestinal Mucosa/cytology , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Lipopolysaccharides/immunology , Macrophages/immunology , Macrophages/metabolism , Male , Neutrophils/immunology , Neutrophils/metabolism , Neutrophils/pathology , Rabbits , Shigella flexneri/growth & development , Shigella flexneri/immunology
16.
Clin Diagn Lab Immunol ; 6(6): 812-8, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10548569

ABSTRACT

The immunoglobulin subclass responses to homologous lipopolysaccharide (LPS) and to cholera toxin (CT) in adult patients infected with Vibrio cholerae O1 and V. cholerae O139 were studied. LPS-specific antibody-secreting cells (ASC) of both the immunoglobulin A1 (IgA1) and IgA2 subclasses were seen, with the IgA1 ASC response predominating in both V. cholerae O1- and O139-infected patients. For antibodies in plasma, by day 11 after onset of disease, all V. cholerae O1- infected patients responded to homologous LPS with the IgA1 subclass (P = 0.001), whereas fewer (68%) responded with the IgA2 subclass (P = 0.007). About 89% of V. cholerae O139-infected patients responded with the IgA1 subclass (P = 0.003), and only 21% responded with the IgA2 subclass (not significant [NS]). Both groups of cholera patients showed significant increases in LPS-specific IgG1, IgG2, and IgG3 antibodies in plasma. In feces, the response to homologous LPS occurred in both groups of patients with the IgA1 and IgA2 subclasses, with 55 to 67% of patients showing a positive response. V. cholerae O1- and O139-infected patients showed CT-specific ASC responses of the different IgG and IgA subclasses in the circulation, and the pattern followed the order IgG1 > IgA1 > IgG2 > IgA2, with low levels of IgG3 and IgG4 ASC. Plasma anti-CT antibody responses in all subclasses were seen by day 11 after onset of disease. Although there were no increases in CT-specific ASC of the IgG3 (NS) and IgG4 (NS) subtypes, there were significant increases of these two subclasses in plasma (P

Subject(s)
B-Lymphocytes/immunology , Cholera Toxin/immunology , Cholera/immunology , Lipopolysaccharides/immunology , Vibrio cholerae/immunology , Adolescent , Adult , Antibodies, Bacterial/analysis , Antibodies, Bacterial/blood , Antigens, Bacterial/immunology , Feces/microbiology , Humans , Immunoglobulin A/analysis , Immunoglobulin A/blood , Immunoglobulin G/analysis , Immunoglobulin G/blood , Male , Middle Aged
17.
Infect Immun ; 67(12): 6234-41, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10569732

ABSTRACT

Immune responses against enterotoxigenic Escherichia coli (ETEC) were examined in Bangladeshi adults with naturally acquired disease and compared to responses in age-matched Bangladeshi volunteers who had been orally immunized with a vaccine consisting of inactivated ETEC bacteria expressing different colonization factor antigens (CFs) and the B subunit of cholera toxin. B-cell responses in duodenal biopsy samples, feces, intestinal washings, and blood were determined. Because most of the patients included in the study were infected with ETEC expressing CS5, immune responses to this CF were studied most extensively. Vaccinees and patients had comparable B-cell responses against this antigen in the duodenum: the median numbers of antibody-secreting cells (ASC) were 3,300 immunoglobulin A (IgA) ASC/10(7) mononuclear cells (MNC) in the patient group (n = 8) and 1,200 IgA ASC/10(7) MNC in the vaccinees (n = 13) (not a significant difference). Similarly, no statistically significant differences were seen in the levels of duodenal B cells directed against enterotoxin among vaccinees and patients. A comparison of the capacities of the various methods used to assess mucosal immune responses revealed a correlation between numbers of circulating B cells and antibody levels in saponin extracts of duodenal biopsy samples (r = 0.58; n = 13; P = 0.04) after vaccination. However, no correlation was seen between blood IgA ASC and duodenal IgA ASC after two doses of vaccine. Still, a correlation between numbers of CF-specific B cells in blood sampled from patients early during infection and numbers of duodenal B cells collected 1 week later was apparent (r = 0.70; n = 10; P = 0.03).


Subject(s)
Antibodies, Bacterial/analysis , Bacterial Proteins/immunology , Bacterial Vaccines/immunology , Duodenum/immunology , Escherichia coli Infections/immunology , Escherichia coli/immunology , Fimbriae Proteins , Adolescent , Adult , Antibody-Producing Cells/immunology , B-Lymphocytes/immunology , Enterotoxins/immunology , Escherichia coli Infections/microbiology , Escherichia coli Vaccines , Female , Humans , Immunity, Mucosal , Immunoglobulin A/analysis , Immunoglobulin A/blood , Male , Middle Aged , Vaccination , Vaccines, Inactivated
18.
Infect Immun ; 66(9): 4507-10, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9712809

ABSTRACT

Enterotoxigenic Escherichia coli (ETEC) strains expressing only coli surface antigen 6 (CS6) have previously been isolated from patients with diarrhea, but the immunogenicity of CS6 has not been established in humans. We have detected CS6-specific immunoglobulin A responses in the feces and blood of patients convalescing from natural ETEC disease and of volunteers given an oral ETEC vaccine.


Subject(s)
Antibodies, Bacterial/analysis , Antigens, Bacterial/immunology , Antigens, Surface/immunology , Bacterial Proteins/immunology , Escherichia coli Proteins , Escherichia coli/immunology , Immunoglobulin A/analysis , Adult , Diarrhea/immunology , Diarrhea/microbiology , Enzyme-Linked Immunosorbent Assay , Escherichia coli Infections/immunology , Humans , Immunoblotting
19.
Infect Immun ; 65(9): 3571-6, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9284121

ABSTRACT

Vibrio cholerae O139 has recently emerged as the second etiologic agent of cholera in Asia. A study was carried out to evaluate the induction of specific immune responses to the organism in V. cholerae O139-infected patients. The immune responses to V. cholerae O139 Bengal were studied in patients by measuring antibody-secreting cells (ASC), as well as vibriocidal and antitoxic antibodies in the circulation. These responses were compared with those in patients with V. cholerae O1 disease. Strong immunoglobulin A (IgA) and IgM ASC responses were seen against the homologous lipopolysaccharide or serogroup of V. cholerae. The magnitude and isotype of the responses were similar in O139- and O1-infected patients. Vibriocidal antibody responses were seen against bacteria of the homologous but not heterologous serogroup, and these responses reflect the lack of cross-protection between the infections caused by the two serogroups. The two groups of patients showed comparable cholera toxin-specific ASC responses, with the IgG isotype dominating over the IgA isotype, as well as comparable antitoxic immune responses in plasma. These results suggest that despite having a polysaccharide capsule, V. cholerae O139 induces systemic and intestine-derived ASC responses in peripheral blood comparable to those seen in patients with V. cholerae O1 disease.


Subject(s)
Cholera/immunology , Vibrio cholerae/immunology , Adult , Antibodies, Bacterial/immunology , Cholera Toxin/immunology , Cross Reactions , Diarrhea/immunology , Diarrhea/microbiology , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Lipopolysaccharides/immunology
20.
Clin Diagn Lab Immunol ; 4(4): 429-34, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9220159

ABSTRACT

The mannose-sensitive hemagglutinin (MSHA) is a type 4 pilus present in Vibrio cholerae O1 strains of the El Tor biotype, as well as in strains of serogroup O139. It has been shown to be a colonization antigen in animal models. The aim of this study was to investigate systemic and local antibody responses to MSHA in adult patients with cholera due to V. cholerae O1 and O139. Twenty-four of 28 (86%) patients with O1 cholera and 11 of 17 (65%) patients with O139 cholera showed significant increases in MSHA-specific immunoglobulin A (IgA) and IgM antibody-secreting cells (ASCs) 7 days after the onset of disease. However, the magnitude of the ASC response in O1 cholera patients was significantly higher than that in the O139 cholera patients in both IgA-producing (P = 0.015) and IgM-producing (P = 0.029) cells. Both groups of patients responded with antibody responses to MSHA in plasma, seroconverting with both IgA (63 to 70% of patients) and IgG (43 to 59% of patients) antibodies. Compared to the MSHA-specific antibody levels determined in healthy controls (n = 10), more than 90% of O1 and O139 cholera patients showed responses to MSHA of both the IgA and the IgG isotypes. About 70% of the patients in both groups also had antibody responses to MSHA in their feces. In summary, we demonstrated that MSHA is immunogenic, giving rise to both systemic and local antibodies in patients with cholera due to both O1 and O139 serogroups.


Subject(s)
Cholera/immunology , Hemagglutinins/immunology , Vibrio cholerae/immunology , Adolescent , Adult , Antibodies, Bacterial/blood , Antibody Specificity , Antigens, Bacterial/immunology , Cholera/diagnosis , Feces/microbiology , Humans , Immunoglobulin A/blood , Immunoglobulin A/isolation & purification , Immunoglobulin G/blood , Immunoglobulin G/isolation & purification , Immunoglobulin M/blood , Immunoglobulin M/isolation & purification , Mannose , Middle Aged , Vibrio cholerae/chemistry
SELECTION OF CITATIONS
SEARCH DETAIL
...