Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.951
Filtrar
1.
J Infect Public Health ; 13(10): 1397-1404, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32712106

RESUMO

Secondary bacterial infections are commonly associated with prior or concomitant respiratory viral infections. Viral infections damage respiratory airways and simultaneously defects both innate and acquired immune response that provides a favorable environment for bacterial growth, adherence, and facilitates invasion into healthy sites of the respiratory tract. Understanding the molecular mechanism of viral-induced secondary bacterial infections will provide us a chance to develop novel and effective therapeutic approaches for disease prevention. The present study describes details about the secondary bacterial infection during viral infections and their immunological changes.The outcome of discussion avails an opportunity to understand possible secondary bacterial infections associated with novel SARS-CoV-2, presently causing pandemic outbreak COVID-19.


Assuntos
Infecções Bacterianas/imunologia , Infecções Bacterianas/virologia , Infecções por Coronavirus/imunologia , Influenza Humana/imunologia , Pneumonia Viral/imunologia , Imunidade Adaptativa , Bactérias/crescimento & desenvolvimento , Aderência Bacteriana , Betacoronavirus , Infecções por Coronavirus/complicações , Humanos , Tolerância Imunológica , Imunidade Inata , Inflamação/complicações , Influenza Humana/complicações , Interações Microbianas , Pandemias , Gravidade do Paciente , Pneumonia Viral/complicações
2.
Int J Antimicrob Agents ; 56(3): 106103, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32712333

RESUMO

This systemic review and meta-analysis aimed to assess the efficacy of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Candidate studies up to 24 May 2020 were identified from PubMed, Cochrane Library, Embase, medRxiv and bioRxiv. Treatment outcomes included mortality, risk of intensive care unit (ICU) admission and the requirement for mechanical ventilation (MV). Seven retrospective studies involving 592 adult patients with severe COVID-19, including 240 in the tocilizumab group and 352 in the control group, were enrolled. All-cause mortality of severe COVID-19 patients among the tocilizumab group was 16.3% (39/240), which was lower than that in the control group (24.1%; 85/352). However, the difference did not reach statistical significance [risk ratio (RR) = 0.62, 95% confidence interval (CI) 0.31-1.22; I2 = 68%]. Additionally, risk of ICU admission was similar between the tocilizumab and control groups (35.1% vs. 15.8%; RR = 1.51, 95% CI 0.33-6.78; I2 = 86%). The requirement for MV was similar between the tocilizumab and control groups (32.4% vs. 28.6%; RR = 0.82, 95% CI 0.14-4.94; I2 = 91%). However, these non-significant differences between the tocilizumab and control groups may have been the result of baseline characteristics of the tocilizumab group, which were more severe than those of the control group. Based on low-quality evidence, there is no conclusive evidence that tocilizumab would provide any additional benefit to patients with severe COVID-19. Therefore, further recommendation of tocilizumab for COVID-19 cases should be halted until high-quality evidence from randomised controlled trials is available.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Antivirais/administração & dosagem , Infecções por Coronavirus/terapia , Fatores Imunológicos/administração & dosagem , Pneumonia Viral/terapia , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Antivirais/efeitos adversos , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/etiologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/mortalidade , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/crescimento & desenvolvimento , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/terapia , Síndrome da Liberação de Citocina/virologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/imunologia , Esquema de Medicação , Humanos , Fatores Imunológicos/efeitos adversos , Unidades de Terapia Intensiva , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/etiologia , Infecções Oportunistas/imunologia , Infecções Oportunistas/mortalidade , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Respiração Artificial , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento
3.
Adv Exp Med Biol ; 1207: 413-423, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671764

RESUMO

Bacterial infection is a common clinical disease that can affect a variety of organs and tissues. Autophagy, as an important part of the innate immune response and adaptive immune response, plays an important role in the defense against bacterial infection. Bacteria can also evade autophagy by destroying or utilizing autophagy virulence proteins or related molecules. Studying the mechanism of autophagy in bacteria and its interaction with cells help to discover new pathogenic mechanisms of bacterial infection. This chapter introduces the possible mechanisms of autophagy during bacterial infections such as Salmonella and Mycobacterium tuberculosis, in order to discover new ways to prevent and control infectious diseases.


Assuntos
Autofagia , Infecções Bacterianas , Autofagia/imunologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Humanos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Salmonella/imunologia , Salmonella/patogenicidade , Virulência
4.
Nat Med ; 26(7): 1125-1134, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32451499

RESUMO

Understanding of the factors governing immune responses in cancer remains incomplete, limiting patient benefit. In this study, we used mass cytometry to define the systemic immune landscape in response to tumor development across five tissues in eight mouse tumor models. Systemic immunity was dramatically altered across models and time, with consistent findings in the peripheral blood of patients with breast cancer. Changes in peripheral tissues differed from those in the tumor microenvironment. Mice with tumor-experienced immune systems mounted dampened responses to orthogonal challenges, including reduced T cell activation during viral or bacterial infection. Antigen-presenting cells (APCs) mounted weaker responses in this context, whereas promoting APC activation rescued T cell activity. Systemic immune changes were reversed with surgical tumor resection, and many were prevented by interleukin-1 or granulocyte colony-stimulating factor blockade, revealing remarkable plasticity in the systemic immune state. These results demonstrate that tumor development dynamically reshapes the composition and function of the immune macroenvironment.


Assuntos
Infecções Bacterianas/imunologia , Neoplasias da Mama/imunologia , Melanoma Experimental/imunologia , Microambiente Tumoral/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Modelos Animais de Doenças , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Humanos , Ativação Linfocitária/imunologia , Melanoma Experimental/genética , Melanoma Experimental/patologia , Camundongos , Linfócitos T/imunologia , Microambiente Tumoral/genética
6.
Cell ; 180(5): 847-861.e15, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32142678

RESUMO

Early life environmental exposure, particularly during perinatal period, can have a life-long impact on organismal development and physiology. The biological rationale for this phenomenon is to promote physiological adaptations to the anticipated environment based on early life experience. However, perinatal exposure to adverse environments can also be associated with adult-onset disorders. Multiple environmental stressors induce glucocorticoids, which prompted us to investigate their role in developmental programming. Here, we report that perinatal glucocorticoid exposure had long-term consequences and resulted in diminished CD8 T cell response in adulthood and impaired control of tumor growth and bacterial infection. We found that perinatal glucocorticoid exposure resulted in persistent alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Consequently, the level of the hormone in adults was significantly reduced, resulting in decreased CD8 T cell function. Our study thus demonstrates that perinatal stress can have long-term consequences on CD8 T cell immunity by altering HPA axis activity.


Assuntos
Infecções Bacterianas/imunologia , Desenvolvimento Embrionário/imunologia , Glucocorticoides/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/genética , Animais , Infecções Bacterianas/genética , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células/efeitos dos fármacos , Dexametasona/farmacologia , Desenvolvimento Embrionário/genética , Feminino , Glucocorticoides/imunologia , Glucocorticoides/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Interleucina-4/farmacologia , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Neoplasias/induzido quimicamente , Neoplasias/genética , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Receptores de Glucocorticoides/genética , Transdução de Sinais/genética
7.
Mol Immunol ; 121: 111-117, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32199210

RESUMO

The immune system protects from infections primarily by detecting and eliminating invading pathogens. This is predominantly mediated by innate immune cells like neutrophils, monocytes and dendritic cells (DCs) expressing specific receptors recognizing pathogen-associated molecular patterns. DC activation by pathogens leads to the initiation of antigen-specific adaptive immune responses, thereby bridging the innate and adaptive immune systems. However, various pathogens have evolved immune evasion strategies to ensure their survival. In this review, we highlight recent findings on how various microorganisms or their structural features affect or modulate DC development and whether this has any consequences for a protective immune response.


Assuntos
Infecções Bacterianas/imunologia , Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Viroses/imunologia , Imunidade Adaptativa , Animais , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Antígenos Virais/imunologia , Antígenos Virais/metabolismo , Infecções Bacterianas/diagnóstico , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Humanos , Tolerância Imunológica , Imunidade Inata , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Monócitos/imunologia , Índice de Gravidade de Doença , Viroses/diagnóstico
8.
Mol Immunol ; 121: 99-110, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32199212

RESUMO

The complement cascade consists of cell bound and serum proteins acting together to protect the host from pathogens, remove cancerous cells and effectively links innate and adaptive immune responses. Despite its usefulness in microbial neutralization and clearance of cancerous cells, excessive complement activation causes an immune imbalance and tissue damage in the host. Hence, a series of complement regulatory proteins present at a higher concentration in blood plasma and on cell surfaces tightly regulate the cascade. The complement cascade can be initiated by B-1 B cell production of natural antibodies. Natural antibodies arise spontaneously without any known exogenous antigenic or microbial stimulus and protect against invading pathogens, clear apoptotic cells, provide tissue homeostasis, and modulate adaptive immune functions. Natural IgM antibodies recognize microbial and cancer antigens and serve as an activator of complement mediated lysis. This review will discuss advances in complement activation and regulation in bacterial and viral infections, and cancer. We will also explore the crosstalk of natural antibodies with bacterial populations and cancer.


Assuntos
Infecções Bacterianas/imunologia , Imunidade Humoral , Imunidade Inata , Neoplasias/imunologia , Viroses/imunologia , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Antígenos Virais/imunologia , Antígenos Virais/metabolismo , Apoptose/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Ativação do Complemento , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Humanos , Imunoglobulina M/imunologia , Imunoglobulina M/metabolismo , Receptores de Complemento/imunologia , Receptores de Complemento/metabolismo , Evasão Tumoral
9.
Pathog Dis ; 78(1)2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32068828

RESUMO

Macrophages play an integral role in host defenses against intracellular bacterial pathogens. A remarkable plasticity allows for adaptation to the needs of the host to orchestrate versatile innate immune responses to a variety of microbial threats. Several bacterial pathogens have adapted to macrophage plasticity and modulate the classical (M1) or alternative (M2) activation bias towards a polarization state that increases fitness for intracellular survival. Here, we summarize the current understanding of the host macrophage and intracellular bacterial interface; highlighting the roles of M1/M2 polarization in host defense and the mechanisms employed by several important intracellular pathogens to modulate macrophage polarization to favor persistence or proliferation. Understanding macrophage polarization in the context of disease caused by different bacterial pathogens is important for the identification of targets for therapeutic intervention.


Assuntos
Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Interações Hospedeiro-Patógeno/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/microbiologia , Macrófagos/fisiologia , Animais , Infecções Bacterianas/metabolismo , Citocinas/metabolismo , Humanos , Imunidade Inata , Imunomodulação
10.
J Immunoassay Immunochem ; 41(2): 152-157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32028862

RESUMO

Q fever, caused by Coxiella burnetii, is an important zoonosis worldwide. Q fever is documented in many parts of the world; however, information on the disease in Ghana is scanty. This study was therefore conducted to provide evidence of exposure of sheep and goats slaughtered at the Kumasi Abattoir to Coxiella burnetii. A total of 350 serum samples collected from 175 sheep and 175 goats were analyzed for the presence of C. burnetii antibodies using a commercial ELISA kit (ID Vet). Results of the study established a seroprevalence of 28.57% in goats, 16.57% in sheep and an overall seroprevalence of 22.29% in sheep and goats; 20.57% for male sheep, 23.86% for female sheep, 26.44% for male goats and 30.68% for female goats. Results showed that goats are more at risk to the infection than sheep however sex is not a risk factor. This study confirms the existence of Q fever in sheep and goats in Ghana hence, the disease should be considered as a public health risk to workers at the abattoir and other stakeholders in the sheep and goat production chain.


Assuntos
Infecções Bacterianas/imunologia , Coxiella burnetii/imunologia , Doenças das Cabras/imunologia , Doenças dos Ovinos/imunologia , Animais , Infecções Bacterianas/sangue , Infecções Bacterianas/microbiologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Gana , Doenças das Cabras/sangue , Doenças das Cabras/microbiologia , Cabras , Masculino , Fatores de Risco , Ovinos , Doenças dos Ovinos/sangue , Doenças dos Ovinos/microbiologia
11.
J Nucl Med ; 61(3): 319-326, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32034110

RESUMO

Rapid and accurate diagnosis of cardiovascular device infection remains a challenge in the clinic. Anatomic imaging tools such as echocardiography and cardiac CT or CT angiography are the first-line modalities for clinically suspected endocarditis given their ability to detect vegetation and perivalvular complications. Accumulating data suggest that functional imaging with 18F-FDG PET/CT has unique merits over anatomic imaging and could potentially diagnose early cardiac device infection before morphologic damage ensues and identify infection sources or bacterial emboli in the rest of the body. Although an abnormal finding on 18F-FDG PET/CT was added to the 2015 guidelines of the European Society of Cardiology as a major criterion for the diagnosis of device-related and prosthetic valve endocarditis, that addition has not been incorporated in the U.S. guidelines. Beyond these clinically available imaging tools, attempts have been made to develop bacteria-targeting tracers for specific infection imaging, which include tracers of bacterial maltodextrin transporter, bacterial thymidine kinase, antibiotics, antimicrobial peptides, bacterial antibodies, bacteriophages, and bacterial DNA/RNA hybrid nucleotide oligomers. Most of the tracers have been studied only in experimental animals, except for radiolabeled antibiotics, which have been examined in humans without success in clinical translation for infection imaging. In this article, we compare the roles of anatomic and functional imaging for cardiac device infection and discuss the pros and cons of 18F-FDG and bacteria-targeting tracers. While anticipating continued investigations for bacteria-specific tracers in the future, we recommend that 18F-FDG PET/CT, which represents the host-pathogen immune response to infection, be used clinically for identifying cardiovascular device infection.


Assuntos
Infecções Bacterianas/diagnóstico por imagem , Infecções Bacterianas/imunologia , Sistema Cardiovascular/microbiologia , Interações Hospedeiro-Patógeno/imunologia , Imagem Molecular/métodos , Infecções Relacionadas à Prótese/diagnóstico por imagem , Infecções Relacionadas à Prótese/imunologia , Sistema Cardiovascular/diagnóstico por imagem , Humanos
12.
J Immunol ; 204(5): 1255-1262, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31941655

RESUMO

Gut bacteria-associated sepsis is a serious concern in patients with gastrointestinal acute radiation syndrome (GIARS). In our previous studies, gut bacteria-associated sepsis caused high mortality rates in mice exposed to 6-9 Gy of γ-rays. IL-12+CD38+ iNOS+ Mϕ (M1Mϕ) located in the bacterial translocation site (mesenteric lymph nodes [MLNs]) of unirradiated mice were characterized as host defense antibacterial effector cells. However, cells isolated from the MLNs of GIARS mice were mostly CCL1+IL-10+LIGHT+miR-27a+ Mϕ (M2bMϕ, inhibitor cells for the M1Mϕ polarization). Reduced long noncoding RNA Gas5 and increased miR-222 expression in MLN-Mϕ influenced by the irradiation were shown to be associated with M2bMϕ polarization. In this study, the mortality of mice exposed to 7 Gy of γ-rays (7 Gy GIARS mice) was completely controlled after the administration of glycyrrhizin (GL), a major active ingredient in licorice root (Glycyrrhiza glabra). Bacterial translocation and subsequent sepsis were minimal in 7 Gy GIARS mice treated with GL. Increased Gas5 RNA level and decreased miR-222 expression were shown in MLN-Mϕ isolated from 7 Gy GIARS mice treated with GL, and these macrophages did not display any properties of M2bMϕ. These results indicate that gut bacteria-associated sepsis in 7 Gy GIARS mice was controlled by the GL through the inhibition of M2bMϕ polarization at the bacteria translocation site. Expression of Ccl1, a gene required for M2bMϕ survival, is silenced in the MLNs of 7 Gy GIARS mice because of Gas5 RNA, which is increased in these cells after the suppression of miR-222 (a Gas5 RNA expression inhibitor) by the GL.


Assuntos
Bactérias/imunologia , Infecções Bacterianas , Fenômenos Fisiológicos Bacterianos , Translocação Bacteriana , Raios gama/efeitos adversos , Ácido Glicirrízico/farmacologia , Intestinos , Macrófagos , MicroRNAs/imunologia , RNA Longo não Codificante/imunologia , Lesões Experimentais por Radiação , Animais , Infecções Bacterianas/imunologia , Infecções Bacterianas/patologia , Infecções Bacterianas/prevenção & controle , Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos , Fenômenos Fisiológicos Bacterianos/imunologia , Fenômenos Fisiológicos Bacterianos/efeitos da radiação , Translocação Bacteriana/efeitos dos fármacos , Translocação Bacteriana/imunologia , Translocação Bacteriana/efeitos da radiação , Intestinos/imunologia , Intestinos/microbiologia , Macrófagos/imunologia , Macrófagos/microbiologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Lesões Experimentais por Radiação/imunologia , Lesões Experimentais por Radiação/microbiologia , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/prevenção & controle , Sepse/imunologia , Sepse/microbiologia , Sepse/patologia , Sepse/prevenção & controle
13.
J Biomed Sci ; 27(1): 9, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900143

RESUMO

Glycoconjugate vaccines based on bacterial capsular polysaccharides (CPS) have been extremely successful in preventing bacterial infections. The glycan antigens for the preparation of CPS based glycoconjugate vaccines are mainly obtained from bacterial fermentation, the quality and length of glycans are always inconsistent. Such kind of situation make the CMC of glycoconjugate vaccines are difficult to well control. Thanks to the advantage of synthetic methods for carbohydrates syntheses. The well controlled glycan antigens are more easily to obtain, and them are conjugated to carrier protein to from the so-call homogeneous fully synthetic glycoconjugate vaccines. Several fully glycoconjugate vaccines are in different phases of clinical trial for bacteria or cancers. The review will introduce the recent development of fully synthetic glycoconjugate vaccine.


Assuntos
Infecções Bacterianas/prevenção & controle , Carboidratos/uso terapêutico , Polissacarídeos/imunologia , Vacinas Sintéticas/imunologia , Antígenos/imunologia , Cápsulas Bacterianas/genética , Cápsulas Bacterianas/imunologia , Infecções Bacterianas/imunologia , Vacinas Bacterianas/química , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/uso terapêutico , Carboidratos/química , Carboidratos/imunologia , Glicoconjugados/química , Glicoconjugados/imunologia , Glicoconjugados/uso terapêutico , Humanos , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/imunologia , Vacinas Conjugadas/química , Vacinas Conjugadas/imunologia , Vacinas Conjugadas/uso terapêutico , Vacinas Sintéticas/química , Vacinas Sintéticas/uso terapêutico
14.
World J Gastroenterol ; 26(2): 199-218, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31988585

RESUMO

BACKGROUND: Rifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis. However, few studies have investigated the effect of rifaximin in cirrhotic patients with refractory ascites. AIM: To evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible mechanism. METHODS: A total of 75 cirrhotic patients with refractory ascites were enrolled in the study (50 in a rifaximin and 25 in a control group). Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics (19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics). All patients received conventional treatment for refractory ascites, while patients in the rifaximin group received oral rifaximin-α 200 mg four times daily for at least 2 wk. The ascites grade, fasting weight, liver and kidney function, and inflammatory factors in the plasma were evaluated before and after treatment. In addition, the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin treatment. The patients were followed for 6 mo. RESULTS: Compared with the control group, the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin (P = 0.011 and 0.009, respectively). The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group (P = 0.048). The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group (P = 0.024). The abundance of Roseburia, Haemophilus, and Prevotella was significantly reduced after rifaximin treatment, while the abundance of Lachnospiraceae_noname, Subdoligranulum, and Dorea decreased and the abundance of Coprobacillus increased after treatment with rifaximin plus intravenous antibiotics. The gene expression of virulence factors was significantly reduced after treatment in both subgroups treated with rifaximin or rifaximin plus intravenous antibiotics. CONCLUSION: Rifaximin mitigates ascites and improves survival of cirrhotic patients with refractory ascites. A possible mechanism is that rifaximin regulates the structure and function of intestinal bacteria, thus improving the systemic inflammatory state.


Assuntos
Antibacterianos/uso terapêutico , Ascite/tratamento farmacológico , Infecções Bacterianas/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Peritonite/tratamento farmacológico , Rifaximina/uso terapêutico , Idoso , Antibacterianos/farmacologia , Ascite/imunologia , Ascite/microbiologia , Ascite/mortalidade , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Resistência a Medicamentos , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/microbiologia , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Peritonite/imunologia , Peritonite/microbiologia , Peritonite/mortalidade , Rifaximina/farmacologia , Resultado do Tratamento
15.
Nat Microbiol ; 5(1): 14-26, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31857733

RESUMO

Microbial pathogens possess an arsenal of strategies to invade their hosts, evade immune defences and promote infection. In particular, bacteria use virulence factors, such as secreted toxins and effector proteins, to manipulate host cellular processes and establish a replicative niche. Survival of eukaryotic organisms in the face of such challenge requires host mechanisms to detect and counteract these pathogen-specific virulence strategies. In this Review, we focus on effector-triggered immunity (ETI) in metazoan organisms as a mechanism for pathogen sensing and distinguishing pathogenic from non-pathogenic microorganisms. For the purposes of this Review, we adopt the concept of ETI formulated originally in the context of plant pathogens and their hosts, wherein specific host proteins 'guard' central cellular processes and trigger inflammatory responses following pathogen-driven disruption of these processes. While molecular mechanisms of ETI are well-described in plants, our understanding of functionally analogous mechanisms in metazoans is still emerging. In this Review, we present an overview of ETI in metazoans and discuss recently described cellular processes that are guarded by the host. Although all pathogens manipulate host pathways, we focus primarily on bacterial pathogens and highlight pathways of effector-triggered immune defence that sense disruption of core cellular processes by pathogens. Finally, we discuss recent developments in our understanding of how pathogens can evade ETI to overcome these host adaptations.


Assuntos
Bactérias/patogenicidade , Infecções Bacterianas/imunologia , Fatores de Virulência/imunologia , Animais , Bactérias/imunologia , Bactérias/metabolismo , Evasão da Resposta Imune , Imunidade Inata , Inflamassomos , Receptores de Reconhecimento de Padrão/metabolismo , Transdução de Sinais/imunologia , Virulência , Fatores de Virulência/metabolismo
16.
J Immunol ; 204(3): 660-670, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31852751

RESUMO

The influx of neutrophils to infection sites is a fundamental step in host defenses against the frequent human pathogen group B Streptococcus (GBS) and other extracellular bacteria. Using a mouse model of GBS-induced peritonitis, we show in this study that the chemokines Cxcl1 and Cxcl2 play distinctive roles in enhancing the recruitment and the antibacterial activities of neutrophils in a manner that is linked to differences in the cellular sources of these mediators. Cell depletion experiments demonstrated that neutrophils make a significant contribution to the in vivo production of Cxcl2 but not Cxcl1. In vitro, neutrophils responded weakly to LPS but released high levels of Cxcl2 after stimulation with GBS or other bacteria. Neutrophil-derived Cxcl2 acted in an autocrinous manner to increase its own production and to enhance antibacterial activities, including the release of oxygen radicals. In both neutrophils and macrophages, the production of Cxcl1/2 largely required the presence of functional UNC93B1, a chaperone protein involved in signaling by endosomal TLRs. Moreover, the phenotype of UNC93B1-defective phagocytes could be recapitulated by the simultaneous absence of TLR7, 9, and 13 but not by the absence of individual TLRs. Collectively, our data show that neutrophils recognize Gram-positive and Gram-negative bacteria by means of multiple phagosomal TLRs, resulting in de novo synthesis of Cxcl2, amplification of neutrophil recruitment, and potentiation of their antibacterial activities. These data may be useful to devise alternative therapeutic strategies aimed at enhancing the recruitment and the functional activities of polymorphonuclear leukocytes during infections caused by antibiotic-resistant bacteria.


Assuntos
Infecções Bacterianas/imunologia , Quimiocina CXCL2/metabolismo , Endossomos/metabolismo , Neutrófilos/imunologia , Peritonite/imunologia , Animais , Modelos Animais de Doenças , Feminino , Humanos , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos , Receptores Toll-Like/metabolismo
17.
Proc Natl Acad Sci U S A ; 117(1): 337-345, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31871151

RESUMO

Out of the 14 avian ß-defensins identified in the Gallus gallus genome, only 3 are present in the chicken egg, including the egg-specific avian ß-defensin 11 (Gga-AvBD11). Given its specific localization and its established antibacterial activity, Gga-AvBD11 appears to play a protective role in embryonic development. Gga-AvBD11 is an atypical double-sized defensin, predicted to possess 2 motifs related to ß-defensins and 6 disulfide bridges. The 3-dimensional NMR structure of the purified Gga-AvBD11 is a compact fold composed of 2 packed ß-defensin domains. This fold is the archetype of a structural family, dubbed herein as avian-double-ß-defensins (Av-DBD). We speculate that AvBD11 emanated from a monodomain gene ancestor and that similar events might have occurred in arthropods, leading to another structural family of less compact DBDs. We show that Gga-AvBD11 displays antimicrobial activities against gram-positive and gram-negative bacterial pathogens, the avian protozoan Eimeria tenella, and avian influenza virus. Gga-AvBD11 also shows cytotoxic and antiinvasive activities, suggesting that it may not only be involved in innate protection of the chicken embryo, but also in the (re)modeling of embryonic tissues. Finally, the contribution of either of the 2 Gga-AvBD11 domains to these biological activities was assessed, using chemically synthesized peptides. Our results point to a critical importance of the cationic N-terminal domain in mediating antibacterial, antiparasitic, and antiinvasive activities, with the C-terminal domain potentiating the 2 latter activities. Strikingly, antiviral activity in infected chicken cells, accompanied by marked cytotoxicity, requires the full-length protein.


Assuntos
Proteínas Aviárias/genética , Embrião de Galinha/imunologia , Galinhas/fisiologia , Desenvolvimento Embrionário/imunologia , beta-Defensinas/genética , Sequência de Aminoácidos , Animais , Proteínas Aviárias/ultraestrutura , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/veterinária , Bioensaio , Embrião de Galinha/crescimento & desenvolvimento , Embrião de Galinha/microbiologia , Embrião de Galinha/parasitologia , Coccidiose/imunologia , Coccidiose/parasitologia , Coccidiose/veterinária , Eimeria tenella/imunologia , Evolução Molecular , Genoma , Imunidade Inata/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Aviária/imunologia , Influenza Aviária/virologia , Ressonância Magnética Nuclear Biomolecular , Filogenia , Domínios Proteicos/genética , Domínios Proteicos/imunologia
18.
Nephrology (Carlton) ; 25(1): 5-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31587409

RESUMO

Infectious complications are common following kidney transplantation and rank in the top five causes of death in patients with allograft function. Over the last 5 years, there has been emerging evidence that changes in the gastrointestinal microbiota following kidney transplantation may play a key role in the pathogenesis of transplant-associated infections. Different factors have emerged which may disrupt the interaction between the gastrointestinal microbiota and the immune system, which may lead to infective complications in kidney transplant recipients. Over the last 5 years, there has been emerging evidence that changes in the gastrointestinal microbiota following kidney transplantation may play a key role in the pathogenesis of transplant-associated infections. This review will discuss the structure and function of the gastrointestinal microbiota, the changes that occur in the gastrointestinal microbiota following kidney transplantation and the factors underpinning these changes, how these changes may lead to transplant-associated infectious complications and potential treatments which may be instituted to mitigate this risk.


Assuntos
Infecções Bacterianas/microbiologia , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Transplante de Rim/efeitos adversos , Infecções Oportunistas/microbiologia , Animais , Infecções Bacterianas/imunologia , Infecções Bacterianas/prevenção & controle , Disbiose , Interações Hospedeiro-Patógeno , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Infecções Oportunistas/imunologia , Infecções Oportunistas/prevenção & controle , Prebióticos/administração & dosagem , Probióticos/administração & dosagem , Fatores de Risco , Simbióticos/administração & dosagem , Resultado do Tratamento
19.
Sci Adv ; 5(11): eaaw4717, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31799388

RESUMO

Increasing evidence indicates that infection-triggered host defenses are regulated by the nervous system. However, the precise mechanisms of this regulation are not well understood. Here, we demonstrate that neuronal G protein-coupled receptor NPR-8 negatively regulates Caenorhabditis elegans defense against pathogen infection by suppressing cuticular collagen expression. NPR-8 controls the dynamics of cuticle structure in response to infection, likely through its regulation of cuticular collagen genes which, in turn, affects the nematode's defense. We further show that the defense activity of NPR-8 is confined to amphid sensory neurons AWB, ASJ, and AWC. It is generally believed that physical barrier defenses are not a response to infections but are part of the body's basic innate defense against pathogens. Our results challenge this view by showing not only that C. elegans cuticle structure dynamically changes in response to infection but also that the cuticle barrier defense is regulated by the nervous system.


Assuntos
Infecções Bacterianas/imunologia , Caenorhabditis elegans/imunologia , Imunidade Inata/imunologia , Sistema Nervoso/imunologia , Receptores Acoplados a Proteínas-G/metabolismo , Animais , Animais Geneticamente Modificados , Colágeno/biossíntese , Escherichia coli/imunologia , Pseudomonas aeruginosa/imunologia , Salmonella enterica/imunologia , Células Receptoras Sensoriais/imunologia , Transdução de Sinais/imunologia , Staphylococcus aureus/imunologia
20.
Nat Commun ; 10(1): 5526, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797922

RESUMO

Type I CRISPR-Cas systems are abundant and widespread adaptive immune systems in bacteria and can greatly enhance bacterial survival in the face of phage infection. Upon phage infection, some CRISPR-Cas immune responses result in bacterial dormancy or slowed growth, which suggests the outcomes for infected cells may vary between systems. Here we demonstrate that type I CRISPR immunity of Pectobacterium atrosepticum leads to suppression of two unrelated virulent phages, ɸTE and ɸM1. Immunity results in an abortive infection response, where infected cells do not survive, but viral propagation is severely decreased, resulting in population protection due to the reduced phage epidemic. Our findings challenge the view of CRISPR-Cas as a system that protects the individual cell and supports growing evidence of abortive infection by some types of CRISPR-Cas systems.


Assuntos
Bactérias/imunologia , Bacteriófagos/imunologia , Sistemas CRISPR-Cas/imunologia , Pectobacterium/imunologia , Bactérias/genética , Bactérias/virologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Bacteriófagos/genética , Bacteriófagos/fisiologia , Sistemas CRISPR-Cas/genética , Viabilidade Microbiana/genética , Viabilidade Microbiana/imunologia , Pectobacterium/genética , Pectobacterium/virologia , Replicação Viral/genética , Replicação Viral/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA