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Floods have a wide range of environmental effects. However, owing to the complex composition of the environment and the numerous factors influencing environmental flood risk, few studies have systematically analyzed the impact of floods on the environment. After reviewing the various impacts of floods on the environment, we summarized them into four indicators (water pollution, erosion and deposition, biomass impact, and biodiversity impact) and analyzed the interrelationships between the four indicators. We then summarized 14 key factors affecting the degree of impact of floods on the environment (flood depth, velocity, duration, sediment concentration, timing of flood, temperature, point source and non-point source, height, age, waterlogging tolerance of plants, migration ability of animals, survival time of animals during floods, species richness, and biomass density) and analyzed their influence mechanisms on each indicator. We then compared the principles, scope of application, accuracy, and limitations of six environmental flood impact evaluation methods and found that the multi-factor evaluation method has great application prospects. Finally, we proposed two recommendations for future research to assess and reduce environmental flood impacts. This review provides a comprehensive understanding of the impact of floods on the environment and a basis for evaluating the impact and formulating measures to mitigate the degree of impact.
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BACKGROUND: Tuberculosis (TB), predominantly caused by Mycobacterium tuberculosis (MTB) infection, remains a prominent global health challenge. Macrophages are the frontline defense against MTB, relying on autophagy for intracellular bacterial clearance. However, MTB can combat and evade autophagy, and it influences macrophage polarization, facilitating immune evasion and promoting infection. We previously found that heparin-binding hemagglutinin (HBHA) inhibits autophagy in A549 cells; however, its role in macrophage autophagy and polarization remains unclear. METHODS: Bacterial cultures, cell cultures, Western blotting, immunofluorescence, macrophage infection assays, siRNA knockdown, and enzyme-linked immunosorbent assay were used to investigate HBHA's impact on macrophages and its relevance in Mycobacterium infection. RESULTS: HBHA inhibited macrophage autophagy. Expression of recombinant HBHA in Mycobacterium smegmatis (rMS-HBHA) inhibited autophagy, promoting bacterial survival within macrophages. Conversely, HBHA knockout in the Mycobacterium bovis bacillus Calmette-Guérin (BCG) mutant (BCG-ΔHBHA) activated autophagy and reduced bacterial survival. Mechanistic investigations revealed that HBHA may inhibit macrophage autophagy through the Toll-like receptor 4-dependent PI3K-AKT-mTOR signaling pathway. Furthermore, HBHA induced macrophage M2 polarization. CONCLUSIONS: Mycobacterium may exploit HBHA to suppress the antimicrobial immune response in macrophages, facilitating intracellular survival and immune evasion through autophagy inhibition and M2 polarization induction. Our findings may help identify novel therapeutic targets and develop more effective treatments against MTB infection.
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Autofagia , Macrófagos , Mycobacterium tuberculosis , Receptor Toll-Like 4 , Macrófagos/inmunología , Macrófagos/microbiología , Macrófagos/metabolismo , Mycobacterium tuberculosis/inmunología , Humanos , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/inmunología , Receptor Toll-Like 4/genética , Transducción de Señal , Animales , Mycobacterium smegmatis/inmunología , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/metabolismo , Tuberculosis/inmunología , Tuberculosis/microbiología , Lectinas/metabolismo , Lectinas/genética , Ratones , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Evasión Inmune , Mycobacterium bovis/inmunología , Células A549 , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
In recent years, dam failures have occurred frequently because of extreme weather, posing a significant threat to downstream residents. The establishment of emergency shelters is crucial for reducing casualties. The selection of suitable shelters depends on key information such as the number and distribution of affected people, and the effective capacity and accessibility of the shelters. However, previous studies on siting shelters did not fully consider population distribution differences at a finer scale. This limitation hinders the accuracy of estimating the number of affected people. In addition, most studies ignored the impact of extreme rainfall on the effective capacity and accessibility of shelters, leading to a low applicability of the shelter selection results. Therefore, in this study, land-use and land-cover change (LUCC) and nighttime lighting data were used to simulate population distribution and determine the number and distribution of affected people. Qualified candidate shelters were obtained based on screening criteria, and their effective capacity and accessibility information under different weather conditions were quantified. Considering factors such as population transfer efficiency, construction cost and shelter capacity constraints, a multi-objective siting model was established and solved using the non-dominated sorting genetic algorithm II (NSGA- II) to obtain the final siting scheme. The method was applied to the Dafangying Reservoir, and the results showed the following: (1) The overall mean relative error (MRE) of the population in the 35 downstream streets was 11.16 %, with good fitting accuracy. The simulation results truly reflect the population distribution. (2) Normal weather screening generated 352 qualified candidate shelters, whereas extreme rainfall weather screening generated 266 candidate shelters. (3) Based on the population distribution and weather factors, four scenarios were set up, with 63, 106, 73, and 131 shelters selected. These two factors have a significant impact on the selection of shelters and the allocation of evacuees, and should be considered in the event of a dam-failure floods.
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Long noncoding RNAs (lncRNAs) have been associated with a variety of biological activities, including immune responses. However, the function of lncRNAs in antiviral innate immune responses are not fully understood. Here, we identified a novel lncRNA, termed dual function regulating influenza virus (DFRV), elevating in a dose- and time-dependent manner during influenza A virus (IAV) infection, which was dependent on the NFκB signaling pathway. Meanwhile, DFRV was spliced into two transcripts post IAV infection, in which DFRV long suppress the viral replication while DFRV short plays the opposite role. Moreover, DFRV regulates IL-1ß and TNF-α via activating several pro-inflammatory signaling cascades, including NFκB, STAT3, PI3K, AKT, ERK1/2 and p38. Besides, DFRV short can inhibit DFRV long expression in a dose-dependent manner. Collectively, our studies reveal that DFRV may act as a potential dual-regulator to preserve innate immune homeostasis in IAV infection.
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BACKGROUND: Helicobacter pylori can cause many kinds of gastric disorders, ranging from gastritis to gastric cancer. Cytotoxin-associated gene A (CagA)+ H. pylori is more likely to cause gastric histopathologic damage than CagA- H. pylori. However, the underlying mechanism needs to be further investigated. MATERIALS AND METHODS: Mice were intragastrically administered equal amounts of CagA+ or CagA- H. pylori. Four weeks later, 24 chemokines in stomachs were measured using a mouse chemokine array, and the phenotypes of the recruited gastric CD4+ T cells were analyzed. The migration pathway was evaluated. Finally, the correlation between each pair among the recruited CD4+ T cell sub-population, H. pylori colonization level, and histopathologic damage score were determined by Pearson correlation analysis. RESULTS: The concentration of chemokines, CCL3 and CX3CL1, were significantly elevated in CagA- H. pylori-infected gastric mucosa than in CagA+ H. pylori-infected gastric mucosa. Among them, CX3CL1 secreted by gastric epithelial cells, which was elicited more effectively by CagA- H. pylori than by the CagA+ strain, dramatically promoted mucosal CD4+ T cell migration. The expression of CX3CR1, the only known receptor of CX3CL1, was upregulated on the surface of gastric CD4+ T cells in CagA- H. pylori-infected stomach. In addition, most of the CX3CR1-positive gastric CD4+ T cells were CD44+CD69-CCR7- effector memory T cells (Tem). Pearson correlation analysis showed that the recruited CX3CR1+CD4+ Tem cell population was negatively correlated with H. pylori colonization level and histopathologic damage score. CONCLUSION: CagA- H. pylori promotes gastric mucosal CX3CR1+CD4+ Tem recruitment in mice.
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Immunosenescence is characterized by an age-related decline in immune system function. Major efforts have been made to identify changes in peripheral blood lymphocyte subsets accompanying immunosenescence in elderly adults. However, the change trends of some lymphocyte subsets with age are still controversial, and populations of advanced ages, such as people in their 80s or 90s, have not yet been thoroughly investigated. To provide further insight, we recruited 957 healthy donors without certain diseases with ages ranging from 20 to 95 years. Peripheral lymphocyte subsets, including T cells, CD4 T cells, CD8 T cells, B cells and NK cells, and the CD4/CD8 ratio were measured by flow cytometry. Additionally, regulatory CD4 T cells with inhibitory functions marked by CD3+CD4+CD25hi and the expression of the costimulatory molecule CD28 on CD8 T cells were evaluated. Sex was considered at the same time. The data indicated that in elderly people, peripheral T (p < 0.001), CD4 T (p < 0.001) and B (p < 0.001) lymphocyte subsets decreased, but the NK cell population (p < 0.001) increased. More regulatory CD4 T cells may imply stronger inhibition in the elderly population. The decreased CD28 expression with age in females verified CD28 to be an immunosenescence marker and the sharply decreased CD28 expression after 75 years in males indicated a rapid immunosenescence at the late life span of the male populations. In addition, our study established reference values for peripheral lymphocyte subsets at different age stages in males and females, which are urgently needed for the clinical management and treatment of geriatric diseases.
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Inmunosenescencia , Anciano , Anciano de 80 o más Años , Relación CD4-CD8 , Femenino , Citometría de Flujo , Humanos , Células Asesinas Naturales , Recuento de Linfocitos , Subgrupos Linfocitarios , Masculino , Subgrupos de Linfocitos TRESUMEN
We present an integrated analysis of urine and serum proteomics and clinical measurements in asymptomatic, mild/moderate, severe and convalescent cases of COVID-19. We identify the pattern of immune response during COVID-19 infection. The immune response is activated in asymptomatic infection, but is dysregulated in mild and severe COVID-19 patients. Our data suggest that the turning point depends on the function of myeloid cells and neutrophils. In addition, immune defects persist into the recovery stage, until 12 months after diagnosis. Moreover, disorders of cholesterol metabolism span the entire progression of the disease, starting from asymptomatic infection and lasting to recovery. Our data suggest that prolonged dysregulation of the immune response and cholesterol metabolism might be the pivotal causative agent of other potential sequelae. Our study provides a comprehensive understanding of COVID-19 immunopathogenesis, which is instructive for the development of early intervention strategies to ameliorate complex disease sequelae.
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Infecciones Asintomáticas , COVID-19/inmunología , Colesterol/metabolismo , Convalecencia , Proteómica , COVID-19/sangre , COVID-19/orina , Estudios de Casos y Controles , Colesterol/sangre , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunidad , Células Mieloides/inmunología , Neutrófilos/inmunología , SARS-CoV-2/aislamiento & purificaciónRESUMEN
When a dam breaks, huge floods will be generated that may inundate urban areas, enterprises, farmlands, and infrastructure and cause giant economic losses. Economic risk criteria are a kind of basis for determining dam risk levels and to decide whether risk control measures should be taken or not. However, compared to loss-of-life risk criteria, much fewer economic risk criteria for dams have been proposed and implemented for two main reasons: (a) The ability of most areas to endure economic losses caused by dam breach changes over time because of the constant development of their economic levels; and (b) Economic development levels in an area are distinct from the levels in other areas, resulting in significant differences in the ability of different areas to endure economic losses caused by a dam breach. Therefore, an equivalent economic scale (EES) that indicates the relative economic level of an area to the whole country in a given period of time is a preferred measure. It was shown in this paper that EES has much more stable values than do ordinary economic measures; therefore, it was taken as the basic index for establishing economic risk criteria. Furthermore, due to the distinct economic loss rates of different industries, the index of industrial economic contribution (IEC) was introduced to determine the correction coefficient to modify the ESS to reflect the potential economic loss of the area to be evaluated. This is the first research that pays careful attention to the change of ability to endure economic losses, in which the established economic risk criteria are applicable over a relatively long time and for different areas based on the consideration of the relative level of the economy and the industrial economic contribution.
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HpaA is considered to be an effective protective antigen for vaccination against Helicobacter pylori (H. pylori) infection. Oral immunization with HpaA significantly decreases bacterial colonization in H. pylori infected mice. In this study, we investigated whether subcutaneous or intranasal immunization with HpaA could protect against H. pylori infection. Mice immunized subcutaneously with HpaA in Complete Freund's adjuvant, but not mice intranasally immunized with HpaA in CpG adjuvant acquired protection against H. pylori infection. However, intranasal immunization with immunodominant epitope peptides in CpG adjuvant protected mice against H. pylori infection, and immunodominant epitope peptides stimulated stronger Th1 responses and mediated more robust protection against H. pylori infection than subdominant ones. Our results suggest that the length of a candidate antigen is critical for particular vaccination routes, and that immunodominant epitope peptides are promising candidates for protection against H. pylori infection through nasal vaccination.
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Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/prevención & control , Helicobacter pylori/inmunología , Helicobacter pylori/patogenicidad , Epítopos Inmunodominantes/inmunología , Péptidos/administración & dosificación , Péptidos/inmunología , Adyuvantes Inmunológicos , Administración Intranasal , Animales , Anticuerpos Antibacterianos/inmunología , Femenino , Citometría de Flujo , Inmunización/métodos , Ratones , Ratones Endogámicos BALB C , Vacunación/métodosRESUMEN
Helicobacter pylori has infected more than half of the world's population, causing gastritis, gastric ulcers, gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer. The oral recombinant Helicobacter pylori vaccine currently used has made great progress in addressing this problem, however, its efficacy and longevity still need to be improved. Th1 and Th17 cells play essential roles in local protection against Helicobacter pylori in the stomach mucosa. Additionally, protective immunodominant antigens are the preferred for a vaccine. In this work, Helicobacter pylori whole cell lysate was separated into 30 groups based on molecular weight by molecular sieve chromatography. The group best promoting CD4 T cells proliferation was selected and evaluated by immunization. The detail proteins were then analyzed by LC-MS/MS and expressed in Escherichia coli. Eleven proteins were selected and the dominant ones were demonstrated. As a result, three protective immunodominant antigens, inosine 5'-monophosphate dehydrogenase, type II citrate synthase, and urease subunit beta, were selected from Helicobacter pylori whole cell. Two of them (inosine 5'-monophosphate dehydrogenase and type II citrate synthase) were newly identified, and one (urease subunit beta) was confirmed as previously reported. The mixture of the three antigens showed satisfactory protective efficiency, with significant lower H. pylori colonization level (P < 0.001) and stronger Th1 (P < 0.001) and Th17 (P < 0.001) responses than PBS control group. Thus, inosine 5'-monophosphate dehydrogenase, type II citrate synthase, and urease subunit beta are three protective antigens inducing dominant Th1 and Th17 responses to defend against Helicobacter pylori infection.
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Adjuvants are widely used to enhance the effects of vaccines against pathogen infections. Interestingly, different adjuvants and vaccination routes usually induce dissimilar immune responses, and can even have completely opposite effects. The mechanism remains unclear. In this study, urease B subunit (UreB), an antigen of Helicobacter pylori (H. pylori) that can induce protective immune responses, was used as a model to vaccinate mice. We investigated the effects of different adjuvants and routes on consequent T cell epitope-specific targeting and protection against H. pylori infection. Comparison of the protective effects of UreB, administered either subcutaneously (sc) or intranasally (in), with the adjuvants AddaVax (sc), Complete Freund's adjuvant (CFA; sc), or CpG oligonucleotide (CpG; sc or in), indicated that only CFA (sc) and CpG (in) were protective. Protective vaccines induced T cells targeting epitopes that differed from that targeted by control vaccination. Subsequent peptide vaccination demonstrated that only two of the identified epitopes were protective: UreB373-385 and UreB317-329. Overall, we found that both adjuvant and vaccination route affected the T cell response repertoire to antigen epitopes. The data obtained in this study contribute to improved characterization of the relationship between adjuvants, routes of vaccination, and epitope-specific T cell response repertoires.
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In mice, antigen-specific CD4+ T cell response is indispensible for the protective immunity against Helicobacter pylori (H. pylori). It has been demonstrated that neuraminyllactose-binding hemagglutinin (HpaA) immunization protected mice from H. pylori infection in a CD4+ T cell dependent manner. However, much remains unclear concerning the human CD4+ T cell responses to HpaA. We conducted a systematic study here to explore the immunodominant, HpaA-specific CD4+ T cell responses in H. pylori infected individuals. We found that HpaA-specific CD4+ T cell responses varied remarkably in their magnitude and had broad epitope-specificity. Importantly, the main responses focused on two regions: HpaA76-105 and HpaA130-159. The HLA-DRB1*0901 restricted HpaA142-159 specific CD4+ T cell response was the most immunodominant response at a population level. The immunodominant epitope HpaA142-159 was naturally presented and highly conserved. We also demonstrated that it was not the broad peptide specificity, but the strength of HpaA specific CD4+ T cell responses associated with gastric diseases potentially caused by H. pylori infection. Such investigation will aid development of novel vaccines against H. pylori infection.
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Adhesinas Bacterianas/inmunología , Linfocitos T CD4-Positivos/inmunología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Cadenas HLA-DRB1/análisis , Infecciones por Helicobacter/complicaciones , Humanos , Gastropatías/inmunologíaRESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) seem to involve in the etiology of chronic spontaneous urticaria (CSU). But studies of the pathogenic mechanism are very little. METHODS: In this study, we detected the serum-specific anti-H. pylori IgG and IgE antibodies in 211 CSU and 137 normal subjects by enzyme-linked immunosorbent assay (ELISA), evaluated the direct activation effects of H. pylori preparations and its protein components on human LAD2 mast cell line in vitro, and analyzed the specific protein ingredients and functions of the most effective H. pylori mixed protein component using liquid chromatography-mass spectrometry and ELISA assay. RESULTS: In CSU patients, the positive rate of anti-H. pylori IgG positive rate was significantly higher than that in normal controls, and the anti-H. pylori IgE levels had no statistical difference between H. pylori-infected patients with and without CSU. Further studies suggested that H. pylori preparations can directly activate human LAD2 mast cell line in a dose-dependent manner and its most powerful protein component was a mixture of 21-35 kDa proteins. Moreover, the 21-35 kDa mixed protein component mainly contained 23 kinds of proteins, which can stimulate the release of histamine, TNF-a, IL-3, IFN-γ, and LTB4 by LAD2 cells in a dose-dependent or time-dependent manner. CONCLUSIONS: A 21-35 kDa mixed protein component should be regarded as the most promising pathogenic factor contributing to the CSU associated with H. pylori infection.
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Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Helicobacter pylori/inmunología , Mastocitos/inmunología , Urticaria/etiología , Adolescente , Adulto , Anciano , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/química , Proteínas Bacterianas/química , Línea Celular , Cromatografía Liquida , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Peso Molecular , Análisis de Secuencia de ADN , Suero/inmunología , Urticaria/patología , Adulto JovenRESUMEN
Helicobacter pylori (H. pylori) infects more than half of the world's population, causing chronic gastritis, peptic ulcers and gastric cancer. Urease B subunit (UreB), a conserved protein of H. pylori, is capable of inducing specific CD4(+) T-cell responses and provides protection against this infection. Previous studies have confirmed the effectiveness of rUreB subunit vaccines in generating CD4(+) T-cell-mediated protection, but less is known regarding the roles of different subtypes of T-cell immunity, such as Th1, Th2 and Th17, particularly the immunodominant epitopes inducing specific CD4(+) T-cell responses, in vaccine-mediated protection. In this study, we demonstrated that the vaccination of BALB/c mice with rUreB resulted in significant antigen-specific Th1 and Th17 immune responses. Importantly, two novel Th epitopes, UreB317-329 and UreB409-421, which are recognized by a major population of CD4(+) T cells, were identified in immunized mice. Our results demonstrated that two novel epitopes can simultaneously induce Th1 and Th17 immune responses; however, only the epitope vaccine-induced CD4(+) T-cells secreting IFN-γ mediated the protection against H. pylori; cells secreting IL-17A did not. Taken together, our results suggest that two novel immunodominant epitopes can induce Th1 and Th17 immune responses, but only the induced Th1 lymphocytes mediate protection against H. pylori.
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Infecciones por Helicobacter/prevención & control , Helicobacter pylori/inmunología , Células TH1/fisiología , Células Th17/fisiología , Vacunación , Adyuvantes Inmunológicos/administración & dosificación , Secuencia de Aminoácidos , Animales , Proteínas Bacterianas/administración & dosificación , Proteínas Bacterianas/química , Proteínas Bacterianas/inmunología , Células Cultivadas , Mapeo Epitopo , Epítopos de Linfocito T/inmunología , Femenino , Adyuvante de Freund/administración & dosificación , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Células TH1/microbiología , Células Th17/microbiología , Ureasa/administración & dosificación , Ureasa/química , Ureasa/inmunologíaRESUMEN
No vaccine against methicillin-resistant Staphylococcus aureus (MRSA) has been currently approved for use in humans. Staphylococcus enterotoxin B (SEB) is one of the most potent MRSA exotoxins. In the present study, we evaluated the efficacy and immunologic mechanisms of an SEB multiple B-cell epitope vaccine against MRSA infection. Synthetic overlapping peptide ELISA identified three novel B-cell immunodominant SEB epitopes (in addition to those previously known): SEB31-48, SEB133-150, and SEB193-210. Six B-cell immunodominant epitopes (amino acid residues 31-48, 97-114, 133-150, 193-210, 205-222, and 247-261) were sufficient to induce robust IgG1/IgG2b-specific protective responses against MRSA infection. Therefore, we constructed a recombinant MRSA SEB-specific multiple B-cell epitope vaccine Polypeptides by combining the six SEB immunodominant epitopes and demonstrated its ability to induce a robust SEB-specific IgG1 response to MRSA, as well as a Th2-directing isotype response. Moreover, Polypeptides-induced antisera stimulated synergetic opsonophagocytosis killing of MRSA. Most importantly, Polypeptides was more effective at clearing the bacteria in MRSA-infected mice than the whole SEB antigen, and was able to successfully protect mice from infection by various clinical MRSA isolates. Altogether, these results support further evaluation of the SEB multiple B-cell epitope-vaccine to address MRSA infection in humans.
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Enterotoxinas/inmunología , Epítopos de Linfocito B/inmunología , Inmunoglobulina G/inmunología , Staphylococcus aureus Resistente a Meticilina/inmunología , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/prevención & control , Animales , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/inmunología , Mapeo Epitopo , Epítopos de Linfocito B/uso terapéutico , Femenino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Resultado del TratamientoRESUMEN
The human gastric pathogen Helicobacter pylori (H. pylori) is a successful colonizer of the stomach. H. pylori infection strongly correlates with the development and progression of chronic gastritis, peptic ulcer disease, and gastric malignances. Vaccination is a promising strategy for preventing H. pylori infection. In this study, we evaluated the candidate antigens heat shock protein A (HspA) and H. pylori γ-glutamyl transpeptidase (GGT) for their effectiveness in development of subunit vaccines against H. pylori infection. rHspA, rGGT, and rHspA-GGT, a fusion protein based on HspA and GGT, were constructed and separately expressed in Escherichia coli and purified. Mice were then immunized intranasally with these proteins, with or without adjuvant. Immunized mice exhibited reduced bacterial colonization in stomach. The highest reduction in bacterial colonization was seen in mice immunized with the fusion protein rHspA-GGT when paired with the mucosal adjuvant LTB. Protection against H. pylori colonization was mediated by a strong systemic and localized humoral immune response, as well as a balanced Th1/Th2 cytokine response. In addition, immunofluorescence microscopy confirmed that rHspA-GGT specific rabbit antibodies were able to directly bind H. pylori in vitro. These results suggest antibodies are essential to the protective immunity associated with rHspA-GGT immunization. In summary, our results suggest HspA and GGT are promising vaccine candidates for protection against H. pylori infection.
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Proteínas Bacterianas/administración & dosificación , Proteínas de Choque Térmico/administración & dosificación , Helicobacter pylori/crecimiento & desarrollo , gamma-Glutamiltransferasa/administración & dosificación , Animales , Anticuerpos Antibacterianos/biosíntesis , Proteínas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/inmunología , Citocinas/biosíntesis , Femenino , Proteínas de Choque Térmico/inmunología , Linfocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/inmunología , gamma-Glutamiltransferasa/inmunologíaRESUMEN
Staphylococcal enterotoxin B (SEB) is one of the most potent Staphylococcus aureus exotoxins (SEs). Due to its conserved sequence and stable structure, SEB might be a good candidate antigen for MRSA vaccines. Although cellular immune responses to SEB are well-characterized, much less is known regarding SEB-specific humoral immune responses, particularly regarding detailed epitope mapping. In this study, we utilized a recombinant nontoxic mutant of SEB (rSEB) and an AlPO4 adjuvant to immunize BALB/c mice and confirmed that rSEB can induce a high antibody level and effective immune protection against MRSA infection. Next, the antisera of immunized mice were collected, and linear B cell epitopes within SEB were finely mapped using a series of overlapping synthetic peptides. Three immunodominant B cell epitopes of SEB were screened by ELISA, including a novel epitope, SEB205-222, and two known epitopes, SEB97-114 and SEB247-261. Using truncated peptides, an ELISA was performed with peptide-KLH antisera, and the core sequence of the three immunodominant B cell epitopes were verified as SEB97-112, SEB207-222, and SEB247-257. In vitro, all of the immunodominant epitope-specific antisera (anti-SEB97-112, anti-SEB207-222 and anti-SEB247-257) were observed to inhibit SEB-induced T cell mitogenesis and cytokine production from splenic lymphocytes of BALB/c mice. The homology analysis indicated that SEB97-112 and SEB207-222 were well-conserved among different Staphylococcus aureus strains. The 3D crystal structure of SEB indicated that SEB97-112 was in the loop region inside SEB, whereas SEB207-222 and SEB247-257 were in the ß-slice region outside SEB. In summary, the fine-mapping of linear B-cell epitopes of the SEB antigen in this study will be useful to understand anti-SEB immunity against MRSA infection further and will be helpful to optimize MRSA vaccine designs that are based on the SEB antigen.