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1.
BMJ ; 367: l5784, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645334

RESUMO

OBJECTIVE: To assess whether severe psychiatric reactions to trauma and other adversities are associated with subsequent risk of life threatening infections. DESIGN: Population and sibling matched cohort study. SETTING: Swedish population. PARTICIPANTS: 144 919 individuals with stress related disorders (post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions) identified from 1987 to 2013 compared with 184 612 full siblings of individuals with a diagnosed stress related disorder and 1 449 190 matched individuals without such a diagnosis from the general population. MAIN OUTCOME MEASURES: A first inpatient or outpatient visit with a primary diagnosis of severe infections with high mortality rates (ie, sepsis, endocarditis, and meningitis or other central nervous system infections) from the Swedish National Patient Register, and deaths from these infections or infections of any origin from the Cause of Death Register. After controlling for multiple confounders, Cox models were used to estimate hazard ratios of these life threatening infections. RESULTS: The average age at diagnosis of a stress related disorder was 37 years (55 541, 38.3% men). During a mean follow-up of eight years, the incidence of life threatening infections per 1000 person years was 2.9 in individuals with a stress related disorder, 1.7 in siblings without a diagnosis, and 1.3 in matched individuals without a diagnosis. Compared with full siblings without a diagnosis of a stress related disorder, individuals with such a diagnosis were at increased risk of life threatening infections (hazard ratio for any stress related disorder was 1.47 (95% confidence intervals1.37 to 1.58) and for PTSD was 1.92 (1.46 to 2.52)). Corresponding estimates in the population based analysis were similar (1.58 (1.51 to 1.65) for any stress related disorder, P=0.09 for difference between sibling and population based comparison, and 1.95 (1.66 to 2.28) for PTSD, P=0.92 for difference). Stress related disorders were associated with all studied life threatening infections, with the highest relative risk observed for meningitis (sibling based analysis 1.63 (1.23 to 2.16)) and endocarditis (1.57 (1.08 to 2.30)). Younger age at diagnosis of a stress related disorder and the presence of psychiatric comorbidity, especially substance use disorders, were associated with higher hazard ratios, whereas use of selective serotonin reuptake inhibitors in the first year after diagnosis of a stress related disorder was associated with attenuated hazard ratios. CONCLUSION: In the Swedish population, stress related disorders were associated with a subsequent risk of life threatening infections, after controlling for familial background and physical or psychiatric comorbidities.


Assuntos
Infecções Bacterianas/epidemiologia , Suscetibilidade a Doenças/imunologia , Transtornos de Estresse Traumático/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/imunologia , Criança , Feminino , Seguimentos , Humanos , Incidência , Masculino , Anamnese , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Índice de Gravidade de Doença , Irmãos , Transtornos de Estresse Traumático/imunologia , Taxa de Sobrevida , Suécia/epidemiologia , Adulto Jovem
2.
F1000Res ; 82019.
Artigo em Inglês | MEDLINE | ID: mdl-31583082

RESUMO

Hypochlorous acid (HOCl; bleach) is a powerful weapon used by our immune system to eliminate invading bacteria. Yet the way HOCl actually kills bacteria and how they defend themselves from its oxidative action have only started to be uncovered. As this molecule induces both protein oxidation and aggregation, bacteria need concerted efforts of chaperones and antioxidants to maintain proteostasis during stress. Recent advances in the field identified several stress-activated chaperones, like Hsp33, RidA, and CnoX, which display unique structural features and play a central role in protecting the bacterial proteome during HOCl stress.


Assuntos
Bactérias/metabolismo , Ácido Hipocloroso/química , Chaperonas Moleculares/metabolismo , Oxidantes/química , Estresse Fisiológico , Infecções Bacterianas/imunologia , Proteínas de Bactérias/metabolismo , Humanos , Oxirredução , Proteólise
3.
J Med Microbiol ; 68(10): 1408-1418, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31418679

RESUMO

Respiratory tract infections are responsible for over 2.8 million deaths per year worldwide. Colonization is the first step in the process of microbes occupying the respiratory tract, which may lead to subsequent infection. Carriage, in contrast, is defined as the occupation of microbial species in the respiratory tract. The duration of carriage may be affected by host immunity, the composition and interactions between members of the microbial community, and the characteristics of colonizing bacteria, including physiology associated with being present in a bacterial biofilm. Numerous vaccines have been implemented to control infections caused by bacteria that can colonize and be subsequently carried. Such vaccines are often species-specific and may target a limited number of strains thereby creating a vacant niche in the upper respiratory tract. Epidemiological changes of bacteria found in both carriage and disease have therefore been widely reported, since the vacant niche is filled by other strains or species. In this review, we discuss the use of carriage-prevalence studies in vaccine evaluation and argue that such studies are essential for (1) examining the epidemiology of carriage before and after the introduction of new vaccines, (2) understanding the dynamics of the respiratory tract flora and (3) identifying the disease potential of emerging strains. In an era of increasing antibiotic resistance, bacterial carriage-prevalence studies are essential for monitoring the impact of vaccination programmes.


Assuntos
Infecções Bacterianas/microbiologia , Vacinas Bacterianas/imunologia , Portador Sadio/microbiologia , Infecções Respiratórias/microbiologia , Animais , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/prevenção & controle , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/genética , Portador Sadio/epidemiologia , Portador Sadio/imunologia , Portador Sadio/prevenção & controle , Humanos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/prevenção & controle , Vacinação
4.
Mol Biotechnol ; 61(8): 602-609, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31161299

RESUMO

Specifically targeted peptide ligands can sabotage pathogenic cell surface proteins and stop increasingly untreatable pathogen infections. Different approaches might be used to sabotage pathogenic cell surface proteins to stop infections. A conjugation treatment uses carefully selected genetically modified plasmids prepared in advance to activate a secondary immune system response neutralizing pathogens with a new, much larger cascade of antibodies. Non-conjugation treatment introduces genetically modified cells into the center of localized pathogen infections to produce peptide ligands; and another non-conjugation treatment introduces only the peptide ligands into the center of localized pathogen infections to sabotage pathogenic cell surface proteins used to specifically infect mammalian cells. Extensive and meticulous plasmid transfer experiments by two separate groups firmly support the feasibility of extremely rapid and thorough plasmid transfer necessary for the conjugation treatment. A third independent group introduced genetically modified bacteria into mammals, including several human volunteers, with safe and effective experimental results, which also firmly supports the feasibility of the first non-conjugation treatment. These three approaches offer several profound advantages compared to treatments using new antibiotics.


Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Animais , Bactérias/química , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Infecções Bacterianas/imunologia , Proteínas de Bactérias/química , Biotecnologia , Sistemas de Liberação de Medicamentos , Humanos , Ligantes , Proteínas de Membrana/química , Peptídeos/farmacologia
5.
PLoS Pathog ; 15(6): e1007893, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31206555

RESUMO

Fatty acids affect a number of physiological processes, in addition to forming the building blocks of membranes and body fat stores. In this study, we uncover a role for the monounsaturated fatty acid oleate in the innate immune response of the nematode Caenorhabditis elegans. From an RNAi screen for regulators of innate immune defense genes, we identified the two stearoyl-coenzyme A desaturases that synthesize oleate in C. elegans. We show that the synthesis of oleate is necessary for the pathogen-mediated induction of immune defense genes. Accordingly, C. elegans deficient in oleate production are hypersusceptible to infection with diverse human pathogens, which can be rescued by the addition of exogenous oleate. However, oleate is not sufficient to drive protective immune activation. Together, these data add to the known health-promoting effects of monounsaturated fatty acids, and suggest an ancient link between nutrient stores, metabolism, and host susceptibility to bacterial infection.


Assuntos
Infecções Bacterianas/imunologia , Caenorhabditis elegans/imunologia , Imunidade Inata/efeitos dos fármacos , Ácidos Oleicos/farmacologia , Animais , Ácidos Oleicos/imunologia
6.
Nat Commun ; 10(1): 2218, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101811

RESUMO

RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance of Streptococcus was higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children.


Assuntos
Infecções Bacterianas/imunologia , Neutrófilos/imunologia , Mucosa Respiratória/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Infecções Bacterianas/microbiologia , Degranulação Celular/imunologia , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Quênia , Metagenômica/métodos , Microbiota/imunologia , Proteômica/métodos , Mucosa Respiratória/citologia , Mucosa Respiratória/microbiologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/isolamento & purificação , Streptococcus/imunologia , Streptococcus/isolamento & purificação
7.
Biochim Biophys Acta Rev Cancer ; 1872(1): 1-10, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31059737

RESUMO

Pyroptosis, a type of inflammatory programmed cell death, is mediated by multiple inflammasomes which can recognize danger signals and activate the secretion of pro-inflammatory cytokines like IL-181 and IL-1ß2. It can induce cancer cell death within the gastrointestinal tract. NLRs3, AIM24, GSDM5 family play important roles in pyroptosis signaling pathways in intestinal cancer such as gastric cancer, colitis-associated colorectal cancer and esophageal cancer, etc. Furthermore, several inflammasomes are elucidated to be involved in mucosal innate immune responses and modulate specific enteric pathogens infection. Precise modulation of inflammasome activation and exploration of potential diagnostic markers can contribute to the diagnosis, prevention and treatment of intestinal tumors and inflammatory or infectious disorders in human patients in the near future.


Assuntos
Infecções Bacterianas/genética , Neoplasias Gastrointestinais/genética , Intestinos/microbiologia , Piroptose/genética , Infecções Bacterianas/complicações , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/imunologia , Neoplasias Gastrointestinais/microbiologia , Humanos , Imunidade Inata/genética , Inflamassomos/genética , Interleucina-18/genética , Interleucina-1beta/genética , Intestinos/patologia
8.
Nanoscale ; 11(22): 10819-10827, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31135010

RESUMO

Myxovirus protein A (MxA) is a biomarker that can be used to distinguish between viral and bacterial infections. While MxA lateral flow assays (LFAs) have been successfully used for viral vs. bacterial differential diagnosis for children, the clinically relevant level of MxA for adults has been reported to be 100 times lower, which is too low for traditional LFAs. We present results applying the use of surface enhanced Raman spectroscopy (SERS) to detect MxA. AuAg nanoshells (AuAg NSs) were used to enhance the Raman signal of mercaptobenzoic acid (4-MBA), enabling readout by SERS. The AuAg NSs were conjugated to antibodies for the biomarker of interest, resulting in a "nanotag", that could be used in a dipstick immunoassay for detection. We first optimized the nanotag parameters using anti-human IgG/human IgG as a model antibody/antigen system, and then demonstrated detection of MxA using anti-MxA antibodies. We show that SERS readout of immunoassays for MxA can quantify MxA levels at clinically relevant levels for adult viral infection.


Assuntos
Anticorpos Antivirais/química , Ouro/química , Imunoglobulina G/química , Nanopartículas Metálicas/química , Proteínas de Resistência a Myxovirus/imunologia , Nanoconchas/química , Infecções por Orthomyxoviridae , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/imunologia , Criança , Humanos , Imunoensaio , Orthomyxoviridae , Infecções por Orthomyxoviridae/diagnóstico , Infecções por Orthomyxoviridae/imunologia , Papel
9.
EBioMedicine ; 43: 587-593, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31056472

RESUMO

BACKGROUND: Autoimmunity and allergy have been associated with decreased number and function of regulatory T-cells (Tregs) and low interleukin-2 (IL-2) levels. We aimed to investigate if the release of IL-2 from peripheral blood mononuclear cells (PBMCs) stimulated with pathogenic airway bacteria was associated with development of allergy-outcomes in early childhood. METHODS: PBMCs were isolated at age 6 months in 331 infants from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) mother-child cohort, and subsequently stimulated with H. influenzae, M. catarrhalis and S. pneumoniae in in vitro cultures. Levels of cytokines (IL-2, IL-10, IFN-γ, TNF-α, IL-5, IL-13 and IL-17A) were determined in the supernatant by electrochemiluminescence immunoassays. The immune profiles were analyzed for association with development of total-IgE, allergic sensitization and rhinitis during the first 7 years of life using regression models and principal component analysis (PCA). FINDINGS: An attenuated IL-2 response to stimulation with H. influenzae (p = 0∙011) and M. catarrhalis (p = 0∙027) was associated with elevated total-IgE at age 7, which was confirmed in a multivariate PCA model including all cytokine measurements (PC2, p = 0∙032). An immune profile with both reduced IL-2 and elevated IL-5 was associated with increased risk of allergic rhinitis (PC3, p = 0∙038). We found no associations with development of allergic sensitization. INTERPRETATION: A reduced IL-2 response from PBMCs exposed to common pathogenic airway bacteria at age 6 months was associated with elevated total-IgE and allergic rhinitis during the first 7 years of life. These findings suggest that suppressed Treg activity in early life may herald onset of allergy in early childhood, which could be a target for low-dose IL-2 trials in the future. FUND: COPSAC is funded by private and public research funds all listed on www.copsac.com.


Assuntos
Bactérias/imunologia , Imunoglobulina E/imunologia , Interleucina-2/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Rinite Alérgica/etiologia , Rinite Alérgica/metabolismo , Fatores Etários , Alérgenos/imunologia , Infecções Bacterianas/complicações , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Estudos de Coortes , Citocinas/metabolismo , Suscetibilidade a Doenças , Feminino , Humanos , Imunização , Imunoglobulina E/sangue , Imunofenotipagem , Lactente , Recém-Nascido , Masculino , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
10.
Int J Mol Sci ; 20(9)2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035661

RESUMO

Inflammasome activation is essential for host immune responses during pathogenic infection and sterile signals insult, whereas excessive activation is injurious. Thus, inflammasome activation is tightly regulated at multiple layers. Ubiquitination is an important post-translational modification for orchestrating inflammatory immune responses during pathogenic infection, and a major target hijacked by pathogenic bacteria for promoting their survival and proliferation. This review summarizes recent insights into distinct mechanisms of the inflammasome activation and ubiquitination process triggered by bacterial infection. We discuss the complex regulatory of inflammasome activation mediated by ubiquitination machinery during bacterial infection, and provide therapeutic approaches for specifically targeting aberrant inflammasome activation.


Assuntos
Infecções Bacterianas/metabolismo , Inflamassomos/metabolismo , Animais , Bactérias/imunologia , Bactérias/metabolismo , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Biomarcadores , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Processamento de Proteína Pós-Traducional , Transdução de Sinais , Ubiquitinação
11.
BMC Res Notes ; 12(1): 241, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036071

RESUMO

OBJECTIVE: Despite the fact that immunization services are offered free of charge in Ethiopia but the coverage of complete vaccination is still low. The aim of the study is to determine incomplete vaccination and associated factors among children aged 12-23 months in Gondar city administration, Northwest Ethiopia, 2018. RESULT: The proportion of incomplete vaccination among children aged 12-23 months in Gondar city adminstration was 24.3% (95% CI 19.3, 29.2). Knowledge about the benefits of vaccination (AOR = 6.1 (95% CI 1.3, 28.9), the age at which the child begins vaccination (AOR = 2.4 (95% CI 1.09, 8.4) time taken to reach nearby health facility and means of transportation to nearby health facility (AOR = 0.22 95% CI 0.06, 0.9) have statistically significant association with incomplete vaccination. In the current study the proportion of incomplete vaccination was found to be high. Increasing the awareness about vaccination for child care givers and further improve caregiver's knowledge towards the benefit of vaccination is important.


Assuntos
Infecções Bacterianas/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Programas de Imunização/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Vacinação/estatística & dados numéricos , Viroses/prevenção & controle , Infecções Bacterianas/imunologia , Infecções Bacterianas/psicologia , Estudos Transversais , Etiópia , Feminino , Humanos , Lactente , Masculino , Mães/psicologia , Cooperação do Paciente/psicologia , Inquéritos e Questionários , Vacinação/psicologia , Cobertura Vacinal/estatística & dados numéricos , Viroses/imunologia , Viroses/psicologia
12.
Fish Shellfish Immunol ; 89: 719-726, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30995543

RESUMO

Myeloid differentiation factor 88 (MyD88) links members of the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) superfamily to the downstream activation of NF-κB as a "bridge" molecular in response to exogenous pathogen, but the function in spotted knifejaw (Oplegnathus. punctatus), a commercial fish in China, is still unknown. We present a functional analysis of spotted knifejaw MyD88 (OppMyD88) with a typical death domain (DD) at the N-terminus and a conservative Toll/IL-1R (TIR) domain at the C-terminus and suggest that MyD88 is important for the activation of TLR-mediated NF-κB with the synergy between domains. Subcellular localization showed that OppMyD88 was distributed in the cytoplasm in a condensed form. Tissues expression profiling analysis showed that OppMyD88 ubiquitously expressed in all tested tissues with the highest expression in the liver, as determined by real-time PCR. The expression of OppMyD88 significantly upregulated in the liver, spleen, kidney and gills within 120 h post Vibrio anguillarum infection. Moreover, we further confirmed that over-expressed OppMyD88 could also induce apoptosis. These results indicate that OppMyD88 might possess important roles in defense against microbial infection and other biological processes in spotted knifejaw similar to those in mammals, which will deepen our understandings in innate immunity of spotted knifejaw.


Assuntos
Proteínas de Peixes/genética , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Fator 88 de Diferenciação Mieloide/genética , Perciformes/genética , Perciformes/imunologia , Transdução de Sinais/genética , Animais , Infecções Bacterianas/imunologia , Infecções Bacterianas/veterinária , Doenças dos Peixes/imunologia , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica/veterinária , Fator 88 de Diferenciação Mieloide/metabolismo
13.
Microbiol Spectr ; 7(2)2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30953433

RESUMO

Successful bacterial colonizers and pathogens have evolved with their hosts and have acquired mechanisms to customize essential processes that benefit their lifestyle. In large part, bacterial survival hinges on shaping the transcriptional signature of the host, a process regulated at the chromatin level. Modifications of chromatin, either on histone proteins or on DNA itself, are common targets during bacterium-host cross talk and are the focus of this article.


Assuntos
Bactérias/metabolismo , Bactérias/patogenicidade , Infecções Bacterianas/metabolismo , Cromatina/metabolismo , Interações Hospedeiro-Patógeno/fisiologia , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Núcleo Celular/metabolismo , DNA/metabolismo , Metilação de DNA , Histonas/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Humanos
14.
Rev Esp Salud Publica ; 932019 Apr 22.
Artigo em Espanhol | MEDLINE | ID: mdl-31006772

RESUMO

Seroprevalence studies are designed in population samples to assess the level and distribution of immunity induced by natural infection of certain infectious agents or by immunization against them. The purpose of the 2nd Seroprevalence Study in Spain is to assess the prevalence and distribution of immune status against vaccine-preventable diseases and generated by natural infection by other microorganisms. Pathologies specifically included in the study are: poliomyelitis, diphtheria, tetanus, pertussis, measles, rubella, mumps, varicella, invasive meningococcal disease by serogroup C, hepatitis A, hepatitis B, hepatitis E, hepatitis C and HIV. The study has a similar design of that conducted in 1996, as it is a descriptive cross-sectional study in resident population of 2 to 80 years of age in Spain. Two-stage conglomerate sampling was carried out on the population aged 2 to 80 years living in Spain, with an initial sample size of 10,000 people. The methodology of the study is described in this article.


Assuntos
Infecções Bacterianas/epidemiologia , Viroses/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/imunologia , Infecções Bacterianas/prevenção & controle , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Imunidade Humoral , Imunogenicidade da Vacina , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Estudos Soroepidemiológicos , Espanha/epidemiologia , Vacinação , Viroses/imunologia , Viroses/prevenção & controle , Adulto Jovem
15.
Int J Mol Sci ; 20(8)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995806

RESUMO

The intestinal epithelium constitutes an indispensable single-layered barrier to protect the body from invading pathogens, antigens or toxins. At the same time, beneficial nutrients and water have to be absorbed by the epithelium. To prevent development of intestinal inflammation or tumour formation, intestinal homeostasis has to be tightly controlled and therefore a strict balance between cell death and proliferation has to be maintained. The proinflammatory cytokine tumour necrosis factor alpha (TNFα) was shown to play a striking role for the regulation of this balance in the gut. Depending on the cellular conditions, on the one hand TNFα is able to mediate cell survival by activating NFκB signalling. On the other hand, TNFα might trigger cell death, in particular caspase-dependent apoptosis but also caspase-independent programmed necrosis. By regulating these cell death and survival mechanisms, TNFα exerts a variety of beneficial functions in the intestine. However, TNFα signalling is also supposed to play a critical role for the pathogenesis of inflammatory bowel disease (IBD), infectious diseases, intestinal wound healing and tumour formation. Here we review the literature about the physiological and pathophysiological role of TNFα signalling for the maintenance of intestinal homeostasis and the benefits and difficulties of anti-TNFα treatment during IBD.


Assuntos
Gastroenteropatias/imunologia , Homeostase , Intestinos/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Anticorpos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/imunologia , Infecções Bacterianas/patologia , Descoberta de Drogas , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/patologia , Homeostase/efeitos dos fármacos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Viroses/tratamento farmacológico , Viroses/imunologia , Viroses/patologia
16.
Cell Physiol Biochem ; 52(2): 280-301, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30816675

RESUMO

Acid sphingomyelinase hydrolyzes sphingomyelin to ceramide and phosphorylcholine. Ceramide molecules spontaneously interact with each other and generate ceramide-enriched membrane domains. These ceramide-enriched domains further fuse, forming large ceramideenriched platforms that participate in the organization of receptors and in the amplification of signaling molecules. Recent studies have suggested several bacteria and bacterial toxins that stimulate the activation and the translocation of acid sphingomyelinase, which leads to the release of ceramide. The acid sphingomyelinase/ceramide system also regulates the internalization of bacteria into the host cell, the subsequent cytokine release, inflammatory response, and initiation of host cell apoptosis. In addition, ceramide has been implicated in the fusion of phagosomes and lysosomes upon bacterial infection. Thus, this system modulates the reorganization of cell membrane receptors and intracellular signaling molecules during bacteria-host interactions. The acid sphingomyelinase and ceramide system may thus serve as a novel therapeutic target for treating infections.


Assuntos
Infecções Bacterianas/imunologia , Toxinas Bacterianas/imunologia , Ceramidas/imunologia , Transdução de Sinais/imunologia , Esfingomielina Fosfodiesterase/imunologia , Animais , Infecções Bacterianas/patologia , Ativação Enzimática/imunologia , Humanos , Inflamação/enzimologia , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia , Lisossomos/imunologia , Lisossomos/microbiologia , Fagossomos/imunologia , Fagossomos/microbiologia
17.
Bull Exp Biol Med ; 166(5): 622-625, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30903500

RESUMO

Over many years, tick-borne infections remain one of the most serious threats to human health worldwide. The immune response to these infections in a human after confirmed bite by an infected carrier at the early stages of infection in the absence of clinical symptoms can be the first indicator of the presence of the infectious agent in the body. During viral infection, the concentration of IL-1α, IL-8, IL-10, IL-17A, and IFNγ increases; superoxide dismutase also increases, in contrast to bacterial infections. A slight decrease in the concentration is observed only for receptor antagonist IL-1Ra. During the infection caused by bacterial pathogens, very similar profiles of the innate human immune response are observed: activation of IL-1α, IL-8, and IFNα and suppression of superoxide dismutase, IL-1Ra, and IL-17A production. It has been demonstrated, that the immune response is triggered immediately after infection, and changes in the concentration of the main cytokines in the blood plasma can be detected as early as on days 2-5 after tick bite. These results can be useful in developing new methods of emergency diagnosis and prevention of tick-borne infections.


Assuntos
Citocinas/metabolismo , Doenças Transmitidas por Carrapatos/imunologia , Animais , Infecções Bacterianas/imunologia , Vírus da Encefalite Transmitidos por Carrapatos/imunologia , Vírus da Encefalite Transmitidos por Carrapatos/patogenicidade , Humanos , Interleucina-17/metabolismo , Interleucina-1alfa/metabolismo , Doenças Transmitidas por Carrapatos/metabolismo
18.
Molecules ; 24(6)2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30871155

RESUMO

The initial contact of pathogens with host cells is usually mediated by their adhesion to glycan structures present on the cell surface in order to enable infection. Furthermore, glycans play important roles in the modulation of the host immune responses to infection. Understanding the carbohydrate-pathogen interactions are of importance for the development of novel and efficient strategies to either prevent, or interfere with pathogenic infection. Synthetic glycopeptides and mimetics thereof are capable of imitating the multivalent display of carbohydrates at the cell surface, which have become an important objective of research over the last decade. Glycopeptide based constructs may function as vaccines or anti-adhesive agents that interfere with the ability of pathogens to adhere to the host cell glycans and thus possess the potential to improve or replace treatments that suffer from resistance. Additionally, synthetic glycopeptides are used as tools for epitope mapping of antibodies directed against structures present on various pathogens and have become important to improve serodiagnostic methods and to develop novel epitope-based vaccines. This review will provide an overview of the most recent advances in the synthesis and application of glycopeptides and glycopeptide mimetics exhibiting a peptide-like backbone in glycobiology.


Assuntos
Infecções Bacterianas/imunologia , Glicopeptídeos/metabolismo , Viroses/imunologia , Animais , Anticorpos/química , Anticorpos/farmacologia , Materiais Biomiméticos/farmacologia , Epitopos/química , Glicosilação , Humanos , Vacinas/farmacologia
19.
Gastroenterology ; 157(1): 149-162, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30905652

RESUMO

BACKGROUND & AIMS: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections. METHODS: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study). RESULTS: Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines. CONCLUSIONS: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.


Assuntos
Albuminas/administração & dosagem , Infecções Bacterianas/imunologia , Citocinas/imunologia , Hipertensão Portal/fisiopatologia , Hipoalbuminemia/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Albumina Sérica/metabolismo , Infecções Bacterianas/complicações , Infecções Bacterianas/fisiopatologia , Estudos de Casos e Controles , Feminino , Hemodinâmica , Humanos , Hipertensão Portal/etiologia , Hipoalbuminemia/etiologia , Hipoalbuminemia/imunologia , Hipoalbuminemia/fisiopatologia , Inflamação , Circulação Hepática , Cirrose Hepática/complicações , Cirrose Hepática/imunologia , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta , Sistema Porta , Estudos Prospectivos , Renina/sangue
20.
Fish Shellfish Immunol ; 88: 441-448, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30872031

RESUMO

Peptidoglycan recognition proteins (PGRPs) are important pattern recognition receptors in the innate immune system of invertebrates. In the study, a short PGRP (designed as RpPGRP) was identified and characterized from the manila clam Ruditapes philippinarum. The open reading frame of RpPGRP encoded a polypeptide of 249-amino acids with a calculated molecular mass of 27.2 kDa and an isoelectric point of 6.62. Multiple alignments and phylogenetic analysis strongly suggested that RpPGRP was a new member of the PGRP superfamily. In non-stimulated clams, RpPGRP exhibited different tissue expression pattern, and highly expressed in hepatopancreas and hemocytes. Expression of RpPGRP transcripts was significantly up-regulated in hemocytes of clams post Vibrio anguillarum or Micrococcus luteus challenge. The recombinant RpPGRP (rRpPGRP) exhibited high affinity to PGN, LPS and zymosan in a concentration-dependent manner. With a broad spectrum of bacterial binding activities, rRpPGRP exhibited strong agglutination activity to Escherichia coli, Vibrio splendidus, V. anguillarum and M. luteus. Furthermore, rRpPGRP exhibited Zn2+-dependent amidase activity and catalyzed the degradation of insoluble PGN. Especially, rRpPGRP exhibited significant antibacterial activity against E. coli and M. luteus. Moreover, the biofilm formation of E. coli could be inhibited after rRpPGRP incubation in the presence of Zn2+. This inhibitory effect of rRpPGRP might attribute to its amide bactericidal activity. Taken together, rRpPGRP played important roles in PGRP-mediated immune defense mechanisms, especially by recognizing antigens and eliminating bacteria.


Assuntos
Infecções Bacterianas/veterinária , Bivalves/imunologia , Proteínas de Transporte/imunologia , Imunidade Inata , Receptores de Reconhecimento de Padrão/imunologia , Animais , Bactérias/patogenicidade , Infecções Bacterianas/imunologia , Proteínas de Transporte/genética , Clonagem Molecular , Hemócitos/imunologia , Filogenia , Receptores de Reconhecimento de Padrão/genética , Alinhamento de Sequência
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