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1.
Front Immunol ; 12: 595343, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717074

RESUMO

Likely as in other viral respiratory diseases, SARS-CoV-2 elicit a local immune response, which includes production and releasing of both cytokines and secretory immunoglobulin (SIgA). Therefore, in this study, we investigated the levels of specific-SIgA for SARS-CoV-2 and cytokines in the airways mucosa 37 patients who were suspected of COVID-19. According to the RT-PCR results, the patients were separated into three groups: negative for COVID-19 and other viruses (NEGS, n = 5); negative for COVID-19 but positive for the presence of other viruses (OTHERS, n = 5); and the positive for COVID-19 (COVID-19, n = 27). Higher specific-SIgA for SARS-CoV-2, IFN-ß, and IFN-γ were found in the COVID-19 group than in the other groups. Increased IL-12p70 levels were observed in OTHERS group as compared to COVID-19 group. When the COVID-19 group was sub stratified according to the illness severity, significant differences and correlations were found for the same parameters described above comparing severe COVID-19 to the mild COVID-19 group and other non-COVID-19 groups. For the first time, significant differences are shown in the airway's mucosa immune responses in different groups of patients with or without respiratory SARS-CoV-2 infection.


Assuntos
Anticorpos Antivirais/metabolismo , Imunoglobulina A/metabolismo , Interferons/metabolismo , Pulmão/patologia , Mucosa Nasal/metabolismo , /fisiologia , Adolescente , Adulto , Idoso , Brasil , Criança , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Adulto Jovem
2.
Nat Commun ; 12(1): 1067, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594081

RESUMO

Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF-dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn's diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas-intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation.


Assuntos
Inflamação/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Glicoproteínas de Membrana/metabolismo , Células Acinares/metabolismo , Células Acinares/patologia , Animais , Colite/metabolismo , Colite/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Fezes , Proteínas de Fluorescência Verde/metabolismo , Humanos , Imunoglobulina A/metabolismo , Mucosa Intestinal/microbiologia , Camundongos Endogâmicos C57BL , Pâncreas/patologia , Proteínas Recombinantes/farmacologia , Fatores de Transcrição/metabolismo , Regulação para Cima/genética
3.
Vet Res ; 52(1): 2, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397461

RESUMO

Porcine epidemic diarrhea (PED) is a coronavirus disease characterized by the rapid spread of severe diarrhea among pigs. PED virus (PEDV) infects and replicates mainly in the epithelial cells of the duodenum, jejunum, ileum and colon. Serum or mucosal IgA antibody levels have been used to predict both vaccine efficacy and the level of protective immunity to enteric infectious diseases in individuals or herds. Details of the B-cell immune response upon PEDV infection, such as the systemic and mucosal PEDV IgA antibody response, the distribution of IgA antibody-secreting cells (ASCs), and their role in virus clearance are not yet clear. In this experimental infection study, we observed similar fluctuations in PEDV IgA antibody levels in serum and intestinal contents of the upper and lower jejunum and ileum, but not fecal samples, over the 4-week experimental course. ASCs that actively secrete PEDV IgA antibody without in vitro stimulation were distributed mainly in the upper jejunum, whereas memory B cells that showed enhanced PEDV IgA antibody production upon in vitro stimulation were observed in mesenteric lymph nodes and the ileum. Our findings will contribute to the development of effective vaccines and diagnostic methods for PEDV.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/veterinária , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos/virologia , Animais , Chlorocebus aethiops , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Fezes/química , Fezes/virologia , Imunoglobulina A/sangue , Imunoglobulina A/química , Imunoglobulina A/metabolismo , Imunoglobulina G/sangue , Mucosa Intestinal/metabolismo , RNA Viral , Suínos , Doenças dos Suínos/sangue , Doenças dos Suínos/imunologia , Células Vero
4.
BMJ Case Rep ; 14(1)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504520

RESUMO

Staphylococcus aureus is a troublesome pathogen, responsible for a broad range of clinical manifestations, ranging from benign skin infections to life-threatening conditions such as endocarditis and osteomyelitis. The kidney can be affected through a rapidly progressive glomerulonephritis mediated by an inflammatory reaction against a superantigen deposited in the glomerulus during the infection's course. This glomerulopathy has a poor prognosis, often leading to chronically impaired kidney function, eventually progressing to end-stage renal disease. Treatment rests on antibiotherapy. Despite the inflammatory role in this disease's pathophysiology, most authors discourage a simultaneous immunosuppressive approach given the concomitant infection. However, there are some reports of success after administration of systemic corticosteroids in these patients. We present a 66-year-old man with a staphylococcus-induced glomerulonephritis brought on by a vascular graft infection, with rapidly deteriorating kidney function despite extraction of the infected graft and 3 weeks of antibiotherapy with achievement of infection control. Kidney function improved after the introduction of corticosteroids. This case highlights the potential role of corticosteroids in selected cases of staphylococcus-induced glomerulonephritis, particularly those in which the infection is under control.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Antibacterianos/uso terapêutico , Prótese Vascular , Glomerulonefrite/tratamento farmacológico , Glucocorticoides/uso terapêutico , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Idoso , Complexo Antígeno-Anticorpo/metabolismo , Hemocultura , Complemento C3/metabolismo , Remoção de Dispositivo , Progressão da Doença , Glomerulonefrite/etiologia , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Humanos , Imunoglobulina A/metabolismo , Masculino , Metilprednisolona/uso terapêutico , Prednisolona/uso terapêutico , Infecções Relacionadas à Prótese/complicações , Infecções Estafilocócicas/complicações , Staphylococcus aureus
5.
Cell Mol Immunol ; 17(11): 1119-1125, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33037400

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been redetected after discharge in some coronavirus disease 2019 (COVID-19) patients. The reason for the recurrent positivity of the test and the potential public health concern due to this occurrence are still unknown. Here, we analyzed the viral data and clinical manifestations of 289 domestic Chinese COVID-19 patients and found that 21 individuals (7.3%) were readmitted for hospitalization after detection of SARS-CoV-2 after discharge. First, we experimentally confirmed that the virus was involved in the initial infection and was not a secondary infection. In positive retests, the virus was usually found in anal samples (15 of 21, 71.4%). Through analysis of the intracellular viral subgenomic messenger RNA (sgmRNA), we verified that positive retest patients had active viral replication in their gastrointestinal tracts (3 of 16 patients, 18.7%) but not in their respiratory tracts. Then, we found that viral persistence was not associated with high viral titers, delayed viral clearance, old age, or more severe clinical symptoms during the first hospitalization. In contrast, viral rebound was associated with significantly lower levels of and slower generation of viral receptor-binding domain (RBD)-specific IgA and IgG antibodies. Our study demonstrated that the positive retest patients failed to create a robust protective humoral immune response, which might result in SARS-CoV-2 persistence in the gastrointestinal tract and possibly in active viral shedding. Further exploration of the mechanism underlying the rebound in SARS-CoV-2 in this population will be crucial for preventing virus spread and developing effective vaccines.


Assuntos
Betacoronavirus/fisiologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Trato Gastrointestinal/virologia , Pneumonia Viral/diagnóstico , Anticorpos Antivirais/metabolismo , Infecções por Coronavirus/imunologia , Epitopos/imunologia , Humanos , Imunidade Humoral , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Pandemias , Pneumonia Viral/imunologia , Ligação Proteica , Domínios Proteicos/imunologia , Testes Sorológicos , Glicoproteína da Espícula de Coronavírus/imunologia , Carga Viral , Eliminação de Partículas Virais
6.
Proc Natl Acad Sci U S A ; 117(38): 23674-23683, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32907933

RESUMO

The gut microbiome has garnered attention as an effective target to boost immunity and improve cancer immunotherapy. We found that B cell-defective (BCD) mice, such as µ-membrane targeted deletion (µMT) and activation-induced cytidine deaminase (AID) knockouts (KOs), have elevated antitumor immunity under specific pathogen-free but not germ-free conditions. Microbial dysbiosis in these BCD mice enriched the type I IFN (IFN) signature in mucosal CD8+ T cells, resulting in up-regulation of the type I IFN-inducible protein stem cell antigen-1 (Sca-1). Among CD8+ T cells, naïve cells predominantly circulate from the gut to the periphery, and those that had migrated from the mesenteric lymph nodes (mLNs) to the periphery had significantly higher expression of Sca-1. The gut-educated Sca-1+ naïve subset is endowed with enhanced mitochondrial activity and antitumor effector potential. The heterogeneity and functional versatility of the systemic naïve CD8+ T cell compartment was revealed by single-cell analysis and functional assays of CD8+ T cell subpopulations. These results indicate one of the potential mechanisms through which microbial dysbiosis regulates antitumor immunity.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Microbioma Gastrointestinal/imunologia , Interferon Tipo I/imunologia , Neoplasias Experimentais/imunologia , Animais , Antígenos Ly/imunologia , Antígenos Ly/metabolismo , Linfócitos B , Linhagem Celular Tumoral , Células Cultivadas , Disbiose/imunologia , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Interferon Tipo I/metabolismo , Linfonodos/citologia , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais/imunologia
7.
Nat Commun ; 11(1): 4198, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826914

RESUMO

COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 virus while the IgG isotype shows no neutralization. Our results suggest that SARS-CoV-2 specific IgA antibodies, such as MAb362, may provide effective immunity against SARS-CoV-2 by inducing mucosal immunity within the respiratory system, a potentially critical feature of an effective vaccine.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Betacoronavirus/imunologia , Imunoglobulina A/imunologia , Peptidil Dipeptidase A/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Animais , Anticorpos Monoclonais/metabolismo , Anticorpos Neutralizantes/metabolismo , Chlorocebus aethiops , Reações Cruzadas , Epitopos , Células HEK293 , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina A Secretora/imunologia , Imunoglobulina A Secretora/metabolismo , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Modelos Moleculares , Mutação , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Vírus da SARS/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero
8.
J Vis Exp ; (161)2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32773765

RESUMO

Gut microbiota exert pleiotropic roles in human health and disease. Fecal microbiota transplantation (FMT) is an effective method to investigate the biological function of intestinal bacteria as a whole or at the species level. Several different FMT methods have been published. Here, we present an FMT protocol that successfully depletes gut microbiota in a matter of days, followed by transplantation of fecal microbiota from fresh or frozen donor intestinal contents to conventional mice. Real time-PCR is applied to test the efficacy of bacterial depletion. Sequencing of the 16S ribosomal RNA (rRNA) is then applied to test the relative abundance and identity of gut microbiota in recipient mice. We also present a flow cytometry-based detection method of immunoglobulin A (IgA)-coated bacteria in the gut.


Assuntos
Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal/imunologia , Imunoglobulina A/metabolismo , Animais , Humanos , Camundongos , Prevalência
9.
Front Immunol ; 11: 1959, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849655

RESUMO

The lung is the vital target organ of coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the majority of patients the most active virus replication seems to be found in the upper respiratory tract, severe cases however suffer from SARS-like disease associated with virus replication in lung tissues. Due to the current lack of suitable anti-viral drugs the induction of protective immunity such as neutralizing antibodies in the lung is the key aim of the only alternative approach-the development and application of SARS-CoV-2 vaccines. However, past experience from experimental animals, livestock, and humans showed that induction of immunity in the lung is limited following application of vaccines at peripheral sides such as skin or muscles. Based on several considerations we therefore propose here to consider the application of a Modified Vaccinia virus Ankara (MVA)-based vaccine to mucosal surfaces of the respiratory tract as a favorable approach to combat COVID-19.


Assuntos
Betacoronavirus/química , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Vírus Vaccinia/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Administração através da Mucosa , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Brônquios/imunologia , Infecções por Coronavirus/virologia , Humanos , Imunoglobulina A/metabolismo , Tecido Linfoide/imunologia , Plasmócitos/imunologia , Pneumonia Viral/virologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Linfócitos T/imunologia , Vacinação , Vacinas Atenuadas/imunologia
10.
Clin Microbiol Infect ; 26(8): 1082-1087, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32473953

RESUMO

OBJECTIVES: To evaluate the diagnostic performance of seven rapid IgG/IgM tests and the Euroimmun IgA/IgG ELISA for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in COVID-19 patients. METHODS: Specificity was evaluated in 103 samples collected before January 2020. Sensitivity and time to seropositivity was evaluated in 167 samples from 94 patients with COVID-19 confirmed with RT-PCR on nasopharyngeal swab. RESULTS: Specificity (confidence interval) of lateral flow assays (LFAs) was ≥91.3% (84.0-95.5) for IgM, ≥90.3% (82.9-94.8) for IgG, and ≥85.4% (77.2-91.1) for the combination IgM OR IgG. Specificity of the ELISA was 96.1% (90.1-98.8) for IgG and only 73.8% (64.5-81.4) for IgA. Sensitivity 14-25 days after the onset of symptoms was between ≥92.1% (78.5-98.0) and 100% (95.7-100) for IgG LFA compared to 89.5% (75.3-96.4) for IgG ELISA. Positivity of IgM OR IgG for LFA resulted in a decrease in specificity compared to IgG alone without a gain in diagnostic performance, except for VivaDiag. The results for IgM varied significantly between the LFAs with an average overall agreement of only 70% compared to 89% for IgG. The average dynamic trend to seropositivity for IgM was not shorter than for IgG. At the time of hospital admission the sensitivity of LFA was <60%. CONCLUSIONS: Sensitivity for the detection of IgG antibodies 14-25 days after the onset of symptoms was ≥92.1% for all seven LFAs compared to 89.5% for the IgG ELISA. The results for IgM varied significantly, and including IgM antibodies in addition to IgG for the interpretation of LFAs did not improve the diagnostic performance.


Assuntos
Anticorpos Antivirais/análise , Antígenos Virais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/imunologia , Testes Diagnósticos de Rotina , Feminino , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Sensibilidade e Especificidade , Fatores de Tempo , Adulto Jovem
11.
PLoS One ; 15(5): e0232739, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32437393

RESUMO

OBJECTIVES: Systemic sclerosis (SSc) is an auto-immune, multi organ disease marked by severe gastrointestinal (GI) involvement and gut dysbiosis. Here, we aimed to determine the safety and efficacy of fecal microbiota transplantation (FMT) using commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in SSc. METHODS: Ten patients with SSc were randomized to ACHIM (n = 5) or placebo (n = 5) in a double-blind, placebo-controlled 16-week pilot. All patients had mild to severe upper and lower GI symptoms including diarrhea, distention/bloating and/or fecal incontinence at baseline. Gastroduodenoscopy transfer of ACHIM or placebo was performed at weeks 0 and 2. Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16. Secondary endpoints included changes in relative abundance of total, immunoglobulin (Ig) A- and IgM-coated fecal bacteria measured by 16s rRNA sequencing. RESULTS: ACHIM side effects were mild and transient. Two placebo controls experienced procedure-related serious adverse events; one developed laryngospasms at week 0 gastroduodenoscopy necessitating study exclusion whilst one encountered duodenal perforation during gastroduodenoscopy at the last study visit (week 16). Decreased bloating, diarrhea and/or fecal incontinence was observed in four of five patients in the FMT group (week 4 or/and 16) and in two of four in the placebo group (week 4 or 16). Relative abundance, richness and diversity of total and IgA-coated and IgM-coated bacteria fluctuated more after FMT, than after placebo. CONCLUSIONS: FMT of commercially-available ACHIM is associated with gastroduodenoscopy complications but reduces lower GI symptoms by possibly altering the gut microbiota in patients with SSc.


Assuntos
Transplante de Microbiota Fecal , Escleroderma Sistêmico/microbiologia , Escleroderma Sistêmico/terapia , Bactérias , Método Duplo-Cego , Ácidos Graxos/metabolismo , Incontinência Fecal/etiologia , Transplante de Microbiota Fecal/efeitos adversos , Fezes/química , Feminino , Humanos , Imunoglobulina A/metabolismo , Imunoglobulina M/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Placebos , Resultado do Tratamento
12.
Nihon Shokakibyo Gakkai Zasshi ; 117(5): 402-412, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32389912

RESUMO

A 68-year-old woman was referred to our hospital due to widespread purpura on her legs. A diagnosis of IgA vasculitis was made based on the findings of a skin biopsy. However, after being admitted to our hospital, abdominal pain and lower gastrointestinal hemorrhaging developed. The purpura disappeared gradually, whereas the abdominal pain migrated and persisted. Treatment with prednisolone was initiated, and the clinical course improved temporarily. However, her severe abdominal symptoms recurred while, in addition, the intestinal tract lesions migrated after the prednisolone dosage was tapered. Therefore, intravenous high-dose methylprednisolone was administered followed by oral steroids. The dose was thereafter carefully tapered, and the steroid dose reduction was successful with this treatment. We herein report the clinical course of the case along with a review of the relevant literature.


Assuntos
Imunoglobulina A/metabolismo , Púrpura de Schoenlein-Henoch , Vasculite , Abdome , Dor Abdominal , Adulto , Idoso , Feminino , Humanos
14.
PLoS One ; 15(4): e0231723, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343704

RESUMO

Understanding the immune responses against Porcine epidemic diarrhea virus (PEDV) is important to prevent infection and to design control strategies. We evaluated both systemic and mucosal immune responses to PEDV in pigs and assessed if prior exposure to virus protects against re-infection. Three-week-old pigs were infected with PEDV and immune response in blood, intestine, and mesenteric lymph node (MLN) was evaluated. At 30 dpi, virus exposed pigs were challenged with a field isolate of PEDV and immune response at 5 d post challenge was evaluated. We found that PEDV RNA persists in the intestine even after fecal shedding of the virus was stopped at 28 dpi and pigs previously exposed to PEDV are protected from virus shedding after re-infection. PEDV infection induced both humoral and cell mediated immune response with an increase in PEDV specific IgA and IgG antibodies in intestine and serum. Flow cytometry analysis showed a significantly higher frequency of B cells and lower frequency of T cells at 4 dpi. The frequency of CD4/CD8 double positive (DP) memory T cells was significantly increased in the MLN of challenged animals. These studies may provide further insights into understanding the mucosal immune response to PEDV and its role in protection against disease.


Assuntos
Anticorpos Antivirais/análise , Infecções por Coronavirus/imunologia , Diarreia/imunologia , Vírus da Diarreia Epidêmica Suína/imunologia , Animais , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/metabolismo , Linfócitos B/imunologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Diarreia/sangue , Diarreia/veterinária , Diarreia/virologia , Resistência à Doença/imunologia , Fezes/microbiologia , Imunidade Celular , Imunidade Humoral , Imunidade nas Mucosas , Imunoglobulina A/análise , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Imunoglobulina G/análise , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/isolamento & purificação , RNA Viral/isolamento & purificação , Suínos , Linfócitos T/imunologia , Eliminação de Partículas Virais
15.
PLoS One ; 15(4): e0230472, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315306

RESUMO

BACKGROUND: Numerous studies have shown that specific components of breast milk, considered separately, are associated with disease status in the mother or the child using univariate analyses. However, very few studies have considered multivariate analysis approaches to evaluate the relationship between multiple breast milk components simultaneously. AIM: Here we aimed at visualizing breast milk component complex interactions in the context of the allergy status of the mother or the child. METHODS: Milk samples were collected from lactating mothers participating in the Leipziger Forschungszentrum für Zivilisationskrankheiten (LIFE) Child cohort in Leipzig, Germany. A total of 156 breast milk samples, collected at 3 months after birth from mother/infant pairs, were analyzed for 51 breast milk components. Correlation, principal component analysis (PCA) and graphical discovery analysis were used. RESULT: Correlations ranging from 0.40 to 0.96 were observed between breast milk fatty acid and breast milk phospholipids levels and correlations ranging from 0 to 0.76 between specific human milk oligosaccharides (HMO) were observed. No separation of the data based on the risk of allergy in the infants was identified using PCA. When graphical discovery analysis was used, dependencies between maternal plasma immunoglobulin E (IgE) level and the breast milk immune marker transforming growth factor-beta 2 (TGF-ß2), between TGF-ß2, breast milk immunoglobulin A (IgA) and TGF-ß1 as well as between breast milk total protein and birth weight were observed. Graphical discovery analysis also exemplifies a possible competition for the fucosyl group between 2'FL, LNFP-I and 3'FL in the HMO group. Additionally, dependencies between immune component IgA and specific HMO (6'SL and blood group A antigen tetraose type 5 or PI-HMO) were identified. CONCLUSION: Graphical discovery analysis applied to complex matrices such as breast milk composition can aid in understanding the complexity of interactions between breast milk components and possible relations to health parameters in the mother or the infant. This approach can lead to novel discoveries in the context of health and diseases such as allergy. Our study thus represents the first attempt to visualize the complexity and the inter-dependency of breast milk components.


Assuntos
Imunoglobulina A/metabolismo , Hipersensibilidade a Leite/etiologia , Leite Humano/química , Oligossacarídeos/metabolismo , Adulto , Aleitamento Materno , Criança , Estudos de Coortes , Dermatite Alérgica de Contato , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Lactação , Metacrilatos/efeitos adversos , Análise de Componente Principal/métodos , Fatores de Crescimento Transformadores/metabolismo
16.
Anim Sci J ; 91(1): e13372, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32285528

RESUMO

Antibacterial factors act as innate immune components, which respond as soon as bacteria enter a living organism. To prevent and treat mastitis in cattle, understanding the concentrations of these substances inside the udder is important; however, they remain to be studied. In this investigation, the concentration of lingual antimicrobial peptide (LAP), S100 protein (S100A7), lactoferrin (LF), and immunoglobulin antibody were measured in the different fractions of foremilk. Lactating Holstein cows were examined, and 10 foremilk fractions were obtained from sequential samples up to 150 ml. The LAP concentrations in milk samples increased until 25 ml. The LF concentrations increased up to the 10 ml fraction, then stabilized at low level after the 50 ml fraction. For S100A7, some fractions had significantly higher (p < .05) concentrations than the 5 or 10 ml fractions. The IgA antibody concentration increased up to the 5 ml fraction, then after 50 ml fraction showed relatively low concentrations. This investigation determined the concentration patterns of LAP, LF, S100A7, and IgA antibody secreted in milk inside the udders of healthy lactating cows as baseline data. These distinct concentration patterns might indicate various protective responses.


Assuntos
Imunoglobulina A/metabolismo , Lactoferrina/metabolismo , Leite/imunologia , Leite/metabolismo , Proteína A7 Ligante de Cálcio S100/metabolismo , beta-Defensinas/metabolismo , Animais , Bovinos , Feminino , Imunidade Inata , Lactação , Glândulas Mamárias Animais/metabolismo
17.
Anim Sci J ; 91(1): e13365, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32285581

RESUMO

The present study was conducted to examine whether colostrum supplementation in peripartum goats increases the antimicrobial peptides in their milk. Goats were orally administered 2 ml of colostrum whey products (colostrum group) or water (control group) daily, from 2 weeks before until 2 weeks after kidding. Body weights of mothers and kids were measured. Blood, milk, and fecal samples were collected from the mothers, and blood samples were collected from the kids. Concentrations of milk antimicrobial peptides (beta-defensin, cathelicidin, lactoferrin, S100A7, lactoperoxidase, and immunoglobulin A [IgA]) were determined. IgA and nutritional parameters (glucose, total cholesterol, triglyceride, ketone bodies, and non-esterified fatty acids) were also determined in the blood of mothers and kids. Milk IgA and lactoferrin concentrations were higher in the colostrum group than in the control group. Conversely, lower milk concentrations of S100A7 were observed in the colostrum group than that in the control group. Plasma IgA concentrations were higher for kids from the colostrum group than for those from the control group. These results suggest that oral administration of colostrum in pregnant goats increases IgA concentration in postpartum milk, which can subsequently improve the health of their kids.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Peptídeos Catiônicos Antimicrobianos/metabolismo , Colostro , Dieta/veterinária , Suplementos Nutricionais , Lactoferrina/metabolismo , Leite/metabolismo , Proteínas do Soro do Leite/administração & dosagem , beta-Defensinas/metabolismo , Administração Oral , Animais , Feminino , Cabras , Imunoglobulina A/metabolismo , Lactoperoxidase/metabolismo , Período Periparto , Gravidez
18.
PLoS One ; 15(3): e0229065, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126095

RESUMO

Porcine Reproductive and Respiratory Syndrome (PRRS) is a complex model of host/virus relationship. Disease control measures often includes "acclimatization", i.e. the exposure of PRRS-naïve gilts and sows to PRRSV-infected pigs and premises before the breeding period. In this respect, we had repeatedly observed an association between PRRSV-specific IgA responses in oral fluids (OF) of gilts and block of PRRSV spread. Therefore, we set out to investigate in vitro the inhibition of PRRSV replication by OF samples with different titers of PRRSV-specific IgA and IgG antibody, using Real-time RT PCR. PRRSV yield reduction in monocyte-derived macrophages was associated with the IgA content in OF samples, whereas the IgG-rich samples were sometimes associated with antibody-dependent enhancement (ADE) of replication. Accordingly, we could discriminate between ADE-positive and ADE-negative PRRSV strains. Next, we separated Ig isotypes in OF samples of PRRSV-infected pigs by means of protein A and size exclusion chromatography. The above results were confirmed by using separated Ig isotypes. Both dimeric and monomeric IgA were associated with the strongest reduction of PRRSV replication. The treatment of pig macrophages with separated OF antibodies before PRRSV infection was also associated with PRRSV yield reduction, along with clear changes of both CD163 and CD169 surface expression. Our results point at a role of mucosal IgA in the control of PRRSV replication by extra- and/or intracellular interaction with PRRSV, as well as by induction of signals leading to a reduced susceptibility of macrophages to PRRSV infection.


Assuntos
Líquidos Corporais/imunologia , Imunoglobulina A/análise , Boca/imunologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Animais , Anticorpos Antivirais/análise , Anticorpos Antivirais/metabolismo , Líquidos Corporais/virologia , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Imunidade nas Mucosas/fisiologia , Imunoglobulina A/metabolismo , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/patologia , Boca/virologia , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Síndrome Respiratória e Reprodutiva Suína/metabolismo , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Reação em Cadeia da Polimerase em Tempo Real , Suínos , Proteínas Virais/genética
19.
Curr Med Sci ; 40(1): 168-171, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32166679

RESUMO

The study investigated the distribution of Epstein-Barr virus (EBV) EA-IgA, VCA-IgA, and EBVNA-IgG antibodies in a local population of Wuhan, China. Chemiluminescence immunoassay (CLIA) was used to detect EBV EA-IgA, VCA-IgA, and EBVNA-IgG antibodies in 972 subjects undergoing physical examination in Wuhan, and the results were analyzed. The detection rate of EBV was positively correlated with age. In the 972 cases, there was significant difference between different genders in the positive rate of VCA-IgA and EBVNA-IgG. Moreover, the positive rate of VCA-IgA and EBVNA-IgG was higher in men ≥ 60 years old than in those < 60 but no significant differences were found in three antibodies among various age groups. Our results suggested that the EBV infection should be intensively monitored in elderly people in Wuhan.


Assuntos
Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/imunologia , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Proteínas do Capsídeo/imunologia , China , Infecções por Vírus Epstein-Barr/imunologia , Antígenos Nucleares do Vírus Epstein-Barr/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Adulto Jovem
20.
PLoS Med ; 17(3): e1003024, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32181756

RESUMO

BACKGROUND: The Vaxxas high-density microarray patch (HD-MAP) consists of a high density of microprojections coated with vaccine for delivery into the skin. Microarray patches (MAPs) offer the possibility of improved vaccine thermostability as well as the potential to be safer, more acceptable, easier to use, and more cost-effective for the administration of vaccines than injection by needle and syringe (N&S). Here, we report a phase I trial using the Vaxxas HD-MAP to deliver a monovalent influenza vaccine that was to the best of our knowledge the first clinical trial to evaluate the safety, tolerability, and immunogenicity of lower doses of influenza vaccine delivered by MAPs. METHODS AND FINDINGS: HD-MAPs were coated with a monovalent, split inactivated influenza virus vaccine containing A/Singapore/GP1908/2015 H1N1 haemagglutinin (HA). Between February 2018 and March 2018, 60 healthy adults (age 18-35 years) in Melbourne, Australia were enrolled into part A of the study and vaccinated with either: HD-MAPs delivering 15 µg of A/Singapore/GP1908/2015 H1N1 HA antigen (A-Sing) to the volar forearm (FA); uncoated HD-MAPs; intramuscular (IM) injection of commercially available quadrivalent influenza vaccine (QIV) containing A/Singapore/GP1908/2015 H1N1 HA (15 µg/dose); or IM injection of H1N1 HA antigen (15 µg/dose). After 22 days' follow-up and assessment of the safety data, a further 150 healthy adults were enrolled and randomly assigned to 1 of 9 treatment groups. Participants (20 per group) were vaccinated with HD-MAPs delivering doses of 15, 10, 5, 2.5, or 0 µg of HA to the FA or 15 µg HA to the upper arm (UA), or IM injection of QIV. The primary objectives of the study were safety and tolerability. Secondary objectives were to assess the immunogenicity of the influenza vaccine delivered by HD-MAP. Primary and secondary objectives were assessed for up to 60 days post-vaccination. Clinical staff and participants were blind as to which HD-MAP treatment was administered and to administration of IM-QIV-15 or IM-A/Sing-15. All laboratory investigators were blind to treatment and participant allocation. Two further groups in part B (5 participants per group), not included in the main safety and immunological analysis, received HD-MAPs delivering 15 µg HA or uncoated HD-MAPs applied to the forearm. Biopsies were taken on days 1 and 4 for analysis of the cellular composition from the HD-MAP application sites. The vaccine coated onto HD-MAPs was antigenically stable when stored at 40°C for at least 12 months. HD-MAP vaccination was safe and well tolerated; any systemic or local adverse events (AEs) were mild or moderate. Observed systemic AEs were mostly headache or myalgia, and local AEs were application-site reactions, usually erythema. HD-MAP administration of 2.5 µg HA induced haemagglutination inhibition (HAI) and microneutralisation (MN) titres that were not significantly different to those induced by 15 µg HA injected IM (IM-QIV-15). HD-MAP delivery resulted in enhanced humoral responses compared with IM injection with higher HAI geometric mean titres (GMTs) at day 8 in the MAP-UA-15 (GMT 242.5, 95% CI 133.2-441.5), MAP-FA-15 (GMT 218.6, 95% CI 111.9-427.0), and MAP-FA-10 (GMT 437.1, 95% CI 254.3-751.3) groups compared with IM-QIV-15 (GMT 82.8, 95% CI 42.4-161.8), p = 0.02, p = 0.04, p < 0.001 for MAP-UA-15, MAP-FA-15, and MAP-FA-10, respectively. Higher titres were also observed at day 22 in the MAP-FA-10 (GMT 485.0, 95% CI 301.5-780.2, p = 0.001) and MAP-UA-15 (367.6, 95% CI 197.9-682.7, p = 0.02) groups compared with the IM-QIV-15 group (GMT 139.3, 95% CI 79.3-244.5). Results from a panel of exploratory immunoassays (antibody-dependent cellular cytotoxicity, CD4+ T-cell cytokine production, memory B cell (MBC) activation, and recognition of non-vaccine strains) indicated that, overall, Vaxxas HD-MAP delivery induced immune responses that were similar to, or higher than, those induced by IM injection of QIV. The small group sizes and use of a monovalent influenza vaccine were limitations of the study. CONCLUSIONS: Influenza vaccine coated onto the HD-MAP was stable stored at temperatures up to 40°C. Vaccination using the HD-MAP was safe and well tolerated and resulted in immune responses that were similar to or significantly enhanced compared with IM injection. Using the HD-MAP, a 2.5 µg dose (1/6 of the standard dose) induced HAI and MN titres similar to those induced by 15 µg HA injected IM. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR.org.au), trial ID 108 ACTRN12618000112268/U1111-1207-3550.


Assuntos
Imunogenicidade da Vacina , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Vacinação , Administração Cutânea , Adolescente , Adulto , Anticorpos Antivirais/sangue , Austrália , Células Cultivadas , Estabilidade de Medicamentos , Feminino , Humanos , Imunoglobulina A/metabolismo , Vacinas contra Influenza/efeitos adversos , Influenza Humana/imunologia , Influenza Humana/virologia , Injeções Intramusculares , Masculino , Saliva/imunologia , Saliva/virologia , Linfócitos T/imunologia , Linfócitos T/virologia , Fatores de Tempo , Adesivo Transdérmico , Resultado do Tratamento , Vacinação/efeitos adversos , Adulto Jovem
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