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1.
Artigo em Inglês | MEDLINE | ID: mdl-33093769

RESUMO

Background and Objectives: Sarcoidosis typically presents with peribronchovascular and perilymphatic nodules on high-resolution computed tomography (HRCT); a miliary pattern is reported but not well described. Design setting: We describe four patients with miliary sarcoidosis and results of a systematic review of all previously reported cases from 1985 onwards. Results: We identified only 27 cases of "miliary" sarcoidosis in the HRCT era. These patients were older (85.2% older than 40 years), had more co-morbidities (72.7%) and were symptomatic compared to "typical" sarcoidosis. Respiratory symptoms were present in 61.9% at diagnosis. Hypercalcemia was seen in 28.5%. On review of HRCT images, only 34.6% (9/26) had a "true miliary" pattern without fissural nodules. In our series, prominent perivascular granulomas were seen on histopathology in all. 44.4% (12/27) had tuberculosis preceding or concurrent to miliary sarcoidosis. Of the eight true associations, tuberculosis preceded sarcoidosis by 52 (median, IQR 36) weeks in six and occurred concurrently in another two. The diagnosis of tuberculosis was clinical in all with concurrent diagnosis of tuberculosis and sarcoidosis. Treatment with steroids had 100% response and 14.2% relapse. Conclusions: A true miliary pattern in the HRCT era is very rare in sarcoidosis and subtle perilymphatic pattern is nearly always seen; this should be labeled "pseudo-miliary". Prominent perivascular granulomas are associated with true miliary pattern. Miliary sarcoidosis patients are older and symptomatic, needing treatment at diagnosis. "Miliary" sarcoidosis may follow treatment for tuberculosis; concurrent cases possibly indicate the difficulty in differentiating both or a "tuberculo-sarcoid" presentation. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 53-65).


Assuntos
Pulmão/diagnóstico por imagem , Sarcoidose Pulmonar/diagnóstico , Tomografia Computadorizada por Raios X , Tuberculose Miliar/diagnóstico , Adulto , Idoso , Antituberculosos/uso terapêutico , Técnicas Bacteriológicas , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Recidiva , Sarcoidose Pulmonar/tratamento farmacológico , Sarcoidose Pulmonar/fisiopatologia , Esteroides/uso terapêutico , Resultado do Tratamento , Tuberculose Miliar/tratamento farmacológico , Tuberculose Miliar/microbiologia , Tuberculose Miliar/fisiopatologia
2.
Crit Care ; 24(1): 537, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867808

RESUMO

During critical illness, there are a multitude of forces such as antibiotic use, mechanical ventilation, diet changes and inflammatory responses that could bring the microbiome out of balance. This so-called dysbiosis of the microbiome seems to be involved in immunological responses and may influence outcomes even in individuals who are not as vulnerable as a critically ill ICU population. It is therefore probable that dysbiosis of the microbiome is a consequence of critical illness and may, subsequently, shape an inadequate response to these circumstances.Bronchoscopic studies have revealed that the carina represents the densest site of bacterial DNA along healthy airways, with a tapering density with further bifurcations. This likely reflects the influence of micro-aspiration as the primary route of microbial immigration in healthy adults. Though bacterial DNA density grows extremely sparse at smaller airways, bacterial signal is still consistently detectable in bronchoalveolar lavage fluid, likely reflecting the fact that lavage via a wedged bronchoscope samples an enormous surface area of small airways and alveoli. The dogma of lung sterility also violated numerous observations that long predated culture-independent microbiology.The body's resident microbial consortia (gut and/or respiratory microbiota) affect normal host inflammatory and immune response mechanisms. Disruptions in these host-pathogen interactions have been associated with infection and altered innate immunity.In this narrative review, we will focus on the rationale and current evidence for a pathogenic role of the lung microbiome in the exacerbation of complications of critical illness, such as acute respiratory distress syndrome and ventilator-associated pneumonia.


Assuntos
Estado Terminal , Disbiose/imunologia , Pulmão/microbiologia , Microbiota , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
PLoS One ; 15(9): e0239668, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970762

RESUMO

We developed an approach for substantial attenuation of Mycobacterium tuberculosis by prolonged culturing under gradually acidifying conditions. Bacteria subjected to acidification lost the capacity to form colonies on solid media, but readily resuscitated their growth in the murine host, providing a useful model to study in vivo development of infection mimicking latent and reactivation tuberculosis (TB) in humans. Here we characterize biomarkers of lung pathology and immune responses triggered by such attenuated bacteria in genetically TB-susceptible and resistant mice. In susceptible I/St mice, CFU counts in lungs and spleens were ~1.5-log higher than in resistant B6 mice, accompanied by diffuse pneumonia and excessive lung infiltration with highly activated CD44+CD62L- T-lymphocytes resulting in death between months 7-9 post challenge. B6 mice were characterized by development of local inflammatory foci, higher production of pro-inflammatory IL-6 and IL-11 cytokines and a more balanced T-cell activation in their lungs. CFU counts remained stable in B6 mice during the whole 18-mo observation period, and all mice survived. Thus, we established a mouse model of fatal reactivation TB vs. indefinite mycobacterial possession after identical challenge and characterized the features of immune responses in the lung tissue underlining these polar phenotypes.


Assuntos
Predisposição Genética para Doença , Interleucinas/metabolismo , Pulmão/imunologia , Ativação Linfocitária , Tuberculose Pulmonar/imunologia , Tuberculose Esplênica/imunologia , Animais , Carga Bacteriana , Células Cultivadas , Feminino , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Interleucinas/genética , Selectina L/genética , Selectina L/metabolismo , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/patogenicidade , Baço/imunologia , Baço/microbiologia , Linfócitos T/imunologia , Tuberculose Pulmonar/genética , Tuberculose Esplênica/genética
5.
BMC Infect Dis ; 20(1): 689, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957986

RESUMO

BACKGROUND: The effect of donor lung colonized bacteria on the prognosis of lung transplantation is not clear. We used the technique of next-generation sequencing (NGS) to detect the colonized bacteria from the lower respiratory tract and analyzed whether the colonized bacteria of donor lung could affect the outcomes of lung transplantation. METHODS: Seventeen patients who underwent lung transplantation from March 2018 to June 2018 at Wuxi People's Hospital affiliated to Nanjing Medical University were included in this study. Twelve cases of donor lung were obtained, and 17 lung transplants were performed, including 12 single lung transplantation and 5 bilateral lung transplantation. The colonized bacteria in the lower lobe tissue of donor lung were detected by NGS, and the bacteria culture method was used to detect the bacteria in the airway secretion before and after the operation. The information of length of extracorporeal membrane oxygenation (ECMO) support, mechanical ventilation time, length of intensive care unit (ICU) stay, duration of fever and length of hospital stay were collected for prognostic analysis. RESULTS: Compared with bacterial culture methods, the positive rate by using NGS in the lungs were higher (52.9% vs 41.2%). Among the patients who were transplanted with donor lungs with detected bacteria by NGS before surgery, only one patient (1/9) developed the same bacteria after lung transplantation. Based on results of NGS and bacterial culture, there was no association between the colonized bacteria in donor lungs and the patients' outcomes of immediate posttransplant period. CONCLUSION: NGS showed more sensitive than bacterial culture for detection of bacteria. The colonized bacteria in different parts of the lung are inconsistent. There is no association between the colonized bacteria in donor lungs and short-term outcome of lung transplantation patients.


Assuntos
Bactérias/genética , Transplante de Pulmão/efeitos adversos , Pulmão/microbiologia , Adulto , Idoso , Bactérias/isolamento & purificação , Oxigenação por Membrana Extracorpórea , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Transplante de Pulmão/métodos , Transplante de Pulmão/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Respiração Artificial , Doadores de Tecidos , Transplantados , Resultado do Tratamento
7.
Am J Physiol Lung Cell Mol Physiol ; 319(4): L675-L682, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877221

RESUMO

Mucosal surfaces are constantly exposed to a microbiome consisting of microorganisms that heavily influence human immunity and health. In the lung these microorganisms consist of bacteria, viruses, and fungi and exist in a relatively low biomass state. Bacterial communities of the lung modulate local inflammation and correlate with changes in pulmonary physiology and clinical outcomes in patients with lung disease. Instrumental to this progress has been the study of these bacterial communities in the pathogenesis of pulmonary fibrosis, a fatal and progressive disease culminating in respiratory failure. Key pathophysiological mechanisms in pulmonary fibrosis include recurrent idiopathic alveolar epithelial injury, unchecked collagen deposition, mucociliary dysfunction due to muc5b overexpression, hypoxia, and altered host defense. These key mechanisms and their related consequences promote severe progressive architectural lung destruction and loss of local homeostasis. As such, pulmonary fibrosis is an appropriate target disease for the study of the lung microbiome. Herein, we discuss recent advances in our understanding of the role of the lung microbiome in the pathogenesis of pulmonary fibrosis. We highlight fundamental clinical observations and mechanistic insights and identify crucial areas for further discovery science. An improved understanding of how the lung microbiome acts to influence outcomes in patients with pulmonary fibrosis will lead to enhanced therapies for this devastating lung disease.


Assuntos
Fibrose Pulmonar Idiopática/patologia , Inflamação/patologia , Pulmão/patologia , Microbiota/fisiologia , Animais , Bactérias/patogenicidade , Progressão da Doença , Humanos , Inflamação/microbiologia , Pulmão/microbiologia
8.
Am J Physiol Lung Cell Mol Physiol ; 319(4): L710-L716, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877224

RESUMO

A rapidly expanding new field of lung research has been produced by the emergence of culture-independent next-generation sequencing technologies. While pulmonary microbiome research lags behind the exploration of the microbiome in other organ systems, the field is maturing and has recently produced multiple exciting discoveries. In this mini-review, we will explore recent advances in our understanding of the lung microbiome and the gut-lung axis from an ecological perspective.


Assuntos
Microbioma Gastrointestinal/fisiologia , Pulmão/microbiologia , Microbiota/fisiologia , Ecossistema , Sequenciamento de Nucleotídeos em Larga Escala , Humanos
10.
PLoS Pathog ; 16(8): e1008741, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32750085

RESUMO

Aspergillus fumigatus is an opportunistic mold that infects patients who are immunocompromised or have chronic lung disease, causing significant morbidity and mortality in these populations. While the factors governing the host response to A. fumigatus remain poorly defined, neutrophil recruitment to the site of infection is critical to clear the fungus. Galectin-3 is a mammalian ß-galactose-binding lectin with both antimicrobial and immunomodulatory activities, however the role of galectin-3 in the defense against molds has not been studied. Here we show that galectin-3 expression is markedly up-regulated in mice and humans with pulmonary aspergillosis. Galectin-3 deficient mice displayed increased fungal burden and higher mortality during pulmonary infection. In contrast to previous reports with pathogenic yeast, galectin-3 exhibited no antifungal activity against A. fumigatus in vitro. Galectin-3 deficient mice exhibited fewer neutrophils in their airways during infection, despite normal numbers of total lung neutrophils. Intravital imaging studies confirmed that galectin-3 was required for normal neutrophil migration to the airspaces during fungal infection. Adoptive transfer experiments demonstrated that stromal rather than neutrophil-intrinsic galectin-3 was necessary for normal neutrophil entry into the airspaces. Live cell imaging studies revealed that extracellular galectin-3 directly increases neutrophil motility. Taken together, these data demonstrate that extracellular galectin-3 facilitates recruitment of neutrophils to the site of A. fumigatus infection, and reveals a novel role for galectin-3 in host defense against fungal infections.


Assuntos
Aspergilose/imunologia , Aspergillus fumigatus/fisiologia , Galectina 3/imunologia , Pulmão/microbiologia , Neutrófilos/citologia , Animais , Aspergilose/genética , Aspergilose/microbiologia , Aspergilose/fisiopatologia , Aspergillus fumigatus/genética , Movimento Celular , Feminino , Galectina 3/genética , Humanos , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-32750662

RESUMO

Cystic fibrosis (CF) is a recessively inherited fatal disease that is the subject of extensive research and ongoing development of therapeutics targeting the defective protein, cystic fibrosis transmembrane conductance regulator (CFTR). Despite progress, the link between CFTR and clinical symptoms is incomplete. The severe CF phenotypes are associated with a deficiency of linoleic acid, which is the precursor of arachidonic acid. The release of arachidonic acid from membranes via phospholipase A2 is the rate-limiting step for eicosanoid synthesis and is increased in CF, which contributes to the observed inflammation. A potential deficiency of docosahexaenoic acid may lead to decreased levels of specialized pro-resolving mediators. This pathophysiology may contribute to an early and sterile inflammation, mucus production, and to bacterial colonization, which further increases inflammation and potentiates the clinical symptoms. Advances in lipid technology will assist in elucidating the role of lipid metabolism in CF, and stimulate therapeutic modulations of inflammation.


Assuntos
Ácido Araquidônico/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/metabolismo , Ácidos Docosa-Hexaenoicos/deficiência , Ácido Linoleico/deficiência , Ácido Araquidônico/deficiência , Fibrose Cística/fisiopatologia , Humanos , Inflamação/metabolismo , Ácido Linoleico/metabolismo , Metabolismo dos Lipídeos , Pulmão/metabolismo , Pulmão/microbiologia , Pulmão/fisiopatologia , Muco/metabolismo
12.
BMC Infect Dis ; 20(1): 635, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847524

RESUMO

BACKGROUND: Data regarding the prevalence of metallo-ß-lactamases (MBLs) among Pseudomonas aeruginosa isolates in cystic fibrosis patients are scarce. Furthermore, there is limited knowledge on the effect of MBL production on patient outcomes. Here we describe a fatal respiratory infection due to P. aeruginosa producing VIM-type MBLs in a lung transplant recipient and the results of the subsequent epidemiological investigation. CASE PRESENTATION: P. aeruginosa isolates collected in the index patient and among patients temporally or spatially linked with the index patient were analyzed in terms of antibiotic susceptibility profile and MBL production. Whole-genome sequencing and phylogenetic reconstruction were also performed for all P. aeruginosa isolates producing VIM-type MBLs. A VIM-producing P. aeruginosa strain was identified in a lung biopsy of a lung transplant recipient with cystic fibrosis. The strain was VIM-1-producer and belonged to the ST308. Despite aggressive treatment, the transplant patient succumbed to the pulmonary infection due to the ST308 strain. A VIM-producing P. aeruginosa strain was also collected from the respiratory samples of a different cystic fibrosis patient attending the same cystic fibrosis center. This isolate harbored the blaVIM-2 gene and belonged to the clone ST175. This patient did not experience an adverse outcome. CONCLUSIONS: This is the first description of a fatal infection due to P. aeruginosa producing VIM-type MBLs in a lung transplant recipient. The circulation of P. aeruginosa isolates harboring MBLs pose a substantial risk to the cystic fibrosis population due to the limited therapeutic options available and their spreading potential.


Assuntos
Antibacterianos/uso terapêutico , Transplante de Pulmão , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/enzimologia , Infecções Respiratórias/tratamento farmacológico , Transplantados , Adulto , Fibrose Cística/cirurgia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Evolução Fatal , Feminino , Humanos , Pulmão/microbiologia , Pulmão/patologia , Testes de Sensibilidade Microbiana , Filogenia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Infecções Respiratórias/microbiologia , beta-Lactamases/genética , beta-Lactamases/metabolismo
13.
Appl Microbiol Biotechnol ; 104(19): 8089-8104, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32813065

RESUMO

Interspecies transmissions of viruses between animals and humans may result in unpredictable pathogenic potential and new transmissible diseases. This mechanism has recently been exemplified by the discovery of new pathogenic viruses, such as the novel severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) pandemic, Middle-East respiratory syndrome-coronavirus epidemic in Saudi Arabia, and the deadly outbreak of Ebola in West Africa. The. SARS-CoV-2 causes coronavirus disease-19 (COVID-19), which is having a massive global impact in terms of economic disruption, and, above all, human health. The disease is characterized by dry cough, fever, fatigue, myalgia, and dyspnea. Other symptoms include headache, sore throat, rhinorrhea, and gastrointestinal disorders. Pneumonia appears to be the most common and severe manifestation of the infection. Currently, there is no vaccine or specific drug for COVID-19. Further, the development of new antiviral requires a considerable length of time and effort for drug design and validation. Therefore, repurposing the use of natural compounds can provide alternatives and can support therapy against COVID-19. In this review, we comprehensively discuss the prophylactic and supportive therapeutic role of probiotics for the management of COVID-19. In addition, the unique role of probiotics to modulate the gut microbe and assert gut homeostasis and production of interferon as an antiviral mechanism is described. Further, the regulatory role of probiotics on gut-lung axis and mucosal immune system for the potential antiviral mechanisms is reviewed and discussed.Key points• Gut microbiota role in antiviral diseases• Factors influencing the antiviral mechanism• Probiotics and Covid-19.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Probióticos/uso terapêutico , Animais , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Trato Gastrointestinal/microbiologia , Humanos , Imunidade nas Mucosas , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/virologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Probióticos/metabolismo , Infecções Respiratórias/microbiologia , Viroses/prevenção & controle , Viroses/terapia , Viroses/transmissão , Vitamina D/fisiologia , Zinco/metabolismo
14.
PLoS One ; 15(8): e0237394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822419

RESUMO

Bordetella pertussis vaccine escape mutants that lack expression of the pertussis antigen pertactin (Prn) have emerged in vaccinated populations in the last 10-20 years. Additionally, clinical isolates lacking another acellular pertussis (aP) vaccine component, filamentous hemagglutinin (FHA), have been found sporadically. Here, we show that both whole-cell pertussis (wP) and aP vaccines induced protection in the lungs of mice, but that the wP vaccine was more effective in nasal clearance. Importantly, bacterial populations isolated from the lungs shifted to an FHA-negative phenotype due to frameshift mutations in the fhaB gene. Loss of FHA expression was strongly selected for in Prn-deficient strains in the lungs following aP but not wP vaccination. The combined loss of Prn and FHA led to complete abrogation of bacterial surface binding by aP-induced serum antibodies. This study demonstrates vaccine- and anatomical site-dependent adaptation of B. pertussis and has major implications for the design of improved pertussis vaccines.


Assuntos
Proteínas da Membrana Bacteriana Externa/metabolismo , Bordetella pertussis/fisiologia , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Hemaglutininas/metabolismo , Fatores de Virulência de Bordetella/metabolismo , Animais , Anticorpos Antibacterianos/imunologia , Bordetella pertussis/imunologia , Regulação da Expressão Gênica , Pulmão/metabolismo , Pulmão/microbiologia , Camundongos , Vacinação , Coqueluche/metabolismo , Coqueluche/patologia , Coqueluche/prevenção & controle
16.
APMIS ; 128(12): 647-653, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32794206

RESUMO

IL-2 is a pro-inflammatory and a Th1 inducing cytokine, which is important for activation of the cell-mediated immunity. IL-2 in serum and sputum has been observed to be reduced in cystic fibrosis (CF) patients. The present IL-2 treatment study of Pseudomonas aeruginosa (PA) lung infected mice was performed in order to evaluate the effect of IL-2 supplement. One hundred-and-twenty female BALB/c mice were divided into three groups: 1) IL-2 treatment/infection (TIG), 2) non-treatment/infection (NTIG), and 3) IL-2 treatment/non-infection (TNIG). The mice were challenged intra-tracheally with PA (PAO579) embedded in seaweed alginate to resemble the biofilm mode of growth. At day 0 and 1, the treatment groups received IL-2 s.c. Mice were killed on day 1 or 2, and cytokine production, lung pathology, and quantitative lung bacteriology were estimated. IL-2 treatment of infected mice reduced the number of mice with signs of macroscopic lung pathology at day 2 (p < 0.05). The reduced macroscopic pathology was paralleled by a reduced IL-1ß and TNF-α. In contrast, an increased PMN response at day 2 was observed in the IL-2 treated mice (p < 0.01). This was preceded by a significantly higher degree of microscopic inflammation at day 1 (p < 0.02). The IL-12 levels decreased in both groups of infected mice at day 2 (p < 0.01), however, significantly more in the IL-2 treated mice (p < 0.02). In accordance, but surprisingly, IFN-γ was significantly reduced in the IL-2 treated PA infected group at day 2 (p < 0.05). The present results indicate that early IL-2 treatment prolongs the PMN response but also reduces pro-inflammatory IL-1ß and TNF-α and macroscopic signs of pathology.


Assuntos
Interleucina-2/administração & dosagem , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/fisiologia , Animais , Fibrose Cística/tratamento farmacológico , Fibrose Cística/imunologia , Fibrose Cística/microbiologia , Fibrose Cística/patologia , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/genética
17.
Gene ; 762: 145042, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32777529

RESUMO

OBJECTIVES: Inhibitory effect of allicin with broad-spectrum antimicrobial activity on A. fumigatus and the regulation mechanism of inflammation and autophagy in vitro and in vivo. METHODS: The corresponding concentration of allicin was prepared according to the needs of the experiment. In vitro, 2 ml 5 × 104 of fungal spores suspension was added to the 6-well plate per hole, and different final concentrations of allicin (1 µl/ml, 2.5 µl/ml, 5 µl/ml, 10 µl/ml, 20 µl/ml, 30 µl/ml) were added. The fungal spores were stained by fluorescent dye SYTO 9 (green) every day, and the spore germination inhibition was detected by flow cytometry in different PH. RAW264.7 cells were cultured and stimulated by A. fumigatus spores for 3 h, then allicin solution was added. Then some cells were stained with ROS probe (green) and hochest33342 (blue). The effect of allicin on ROS was observed by fluorescence microscope. The other part of cells extracted protein from cell lysate and detected the effect of allicin on inflammatory factors and autophagy by Western-blotting. The green and red spots of RAW264.7 cells stably transfected with GFP-RFP-LC3 were observed by fluorescence microscopy. In vivo, A. fumigatus spore was injected intratracheally into mice, then allicin was injected intravenously at a concentration of 5 mg/kg/day for 7 consecutive days. The survival status, pulmonary fungal load and weight of mice was recorded continuously for 30 days and detected the changes of lung by pathological examination and immunohistochemistry. RESULTS: In vitro, allicin significantly inhibited the spore germination of A. fumigatus within 24 h in a dose-dependent manner and it had a stable inhibition on the spore germination of A. fumigatus in acidic environment. Cell experiments showed that allicin inhibited intracellular spore germination by inhibiting ROS production, inflammation and autophagy. In the animal experiment, the survival rate and body weight of allicin injection group were higher than that of non injection group, while the spore load of lung was lower than that of non injection group (P < 0.05). CONCLUSIONS: These results support that allicin reduces inflammation and autophagy resistance to A. fumigatus infection, It also provides a possible treatment for Aspergillus infectious diseases, i.e. early anti-inflammation, antibiotics or drugs that inhibit excessive autophagy.


Assuntos
Anti-Inflamatórios/uso terapêutico , Aspergilose/tratamento farmacológico , Autofagia , Depuradores de Radicais Livres/uso terapêutico , Ácidos Sulfínicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Aspergillus fumigatus/patogenicidade , Aspergillus fumigatus/fisiologia , Feminino , Depuradores de Radicais Livres/farmacologia , Pulmão/metabolismo , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Esporos Fúngicos/efeitos dos fármacos , Ácidos Sulfínicos/farmacologia
18.
PLoS Pathog ; 16(8): e1008632, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32790739

RESUMO

Lymph nodes, particularly thoracic lymph nodes, are among the most common sites of extrapulmonary tuberculosis (TB). However, Mycobacterium tuberculosis (Mtb) infection in these organs is understudied. Aside from being sites of initiation of the adaptive immune system, lymph nodes also serve as niches of Mtb growth and persistence. Mtb infection results in granuloma formation that disrupts and-if it becomes large enough-replaces the normal architecture of the lymph node that is vital to its function. In preclinical models, successful TB vaccines appear to prevent spread of Mtb from the lungs to the lymph nodes. Reactivation of latent TB can start in the lymph nodes resulting in dissemination of the bacteria to the lungs and other organs. Involvement of the lymph nodes may improve Bacille Calmette-Guerin (BCG) vaccine efficacy. Lastly, drug penetration to the lymph nodes is poor compared to blood, lung tissue, and lung granulomas. Future studies on evaluating the efficacy of vaccines and anti-TB drug treatments should include consideration of the effects on thoracic lymph nodes and not just the lungs.


Assuntos
Pulmão/imunologia , Linfonodos/imunologia , Mycobacterium tuberculosis/imunologia , Vacinas contra a Tuberculose/imunologia , Tuberculose/imunologia , Tuberculose/patologia , Animais , Humanos , Pulmão/microbiologia , Linfonodos/microbiologia , Mycobacterium tuberculosis/patogenicidade , Tuberculose/microbiologia , Tuberculose/prevenção & controle
19.
PLoS Pathog ; 16(8): e1008761, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32790758

RESUMO

The virus-bacterial synergism implicated in secondary bacterial infections caused by Streptococcus pneumoniae following infection with epidemic or pandemic influenza A virus (IAV) is well documented. However, the molecular mechanisms behind such synergism remain largely ill-defined. In pneumocytes infected with influenza A virus, subsequent infection with S. pneumoniae leads to enhanced pneumococcal intracellular survival. The pneumococcal two-component system SirRH appears essential for such enhanced survival. Through comparative transcriptomic analysis between the ΔsirR and wt strains, a list of 179 differentially expressed genes was defined. Among those, the clpL protein chaperone gene and the psaB Mn+2 transporter gene, which are involved in the stress response, are important in enhancing S. pneumoniae survival in influenza-infected cells. The ΔsirR, ΔclpL and ΔpsaB deletion mutants display increased susceptibility to acidic and oxidative stress and no enhancement of intracellular survival in IAV-infected pneumocyte cells. These results suggest that the SirRH two-component system senses IAV-induced stress conditions and controls adaptive responses that allow survival of S. pneumoniae in IAV-infected pneumocytes.


Assuntos
Proteínas de Bactérias/metabolismo , Coinfecção/mortalidade , Vírus da Influenza A/patogenicidade , Influenza Humana/mortalidade , Pulmão/patologia , Infecções Pneumocócicas/mortalidade , Streptococcus pneumoniae/patogenicidade , Proteínas de Bactérias/genética , Sobrevivência Celular , Coinfecção/epidemiologia , Humanos , Influenza Humana/microbiologia , Influenza Humana/patologia , Influenza Humana/virologia , Pulmão/microbiologia , Pulmão/virologia , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/patologia , Infecções Pneumocócicas/virologia , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Streptococcus pneumoniae/metabolismo , Estresse Fisiológico , Virulência
20.
Emerg Microbes Infect ; 9(1): 1958-1964, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32815458

RESUMO

Objectives Severe or critical COVID-19 is associated with intensive care unit admission, increased secondary infection rate, and would lead to significant worsened prognosis. Risks and characteristics relating to secondary infections in severe COVID-19 have not been described. Methods Severe and critical COVID-19 patients from Shanghai were included. We collected lower respiratory, urine, catheters, and blood samples according to clinical necessity and culture and mNGS were performed. Clinical and laboratory data were archived. Results We found 57.89% (22/38) patients developed secondary infections. The patient receiving invasive mechanical ventilation or in critical state has a higher chance of secondary infections (P<0.0001). The most common infections were respiratory, blood-stream and urinary infections, and in respiratory infections, the most detected pathogens were gram-negative bacteria (26, 50.00%), following by gram-positive bacteria (14, 26.92%), virus (6, 11.54%), fungi (4, 7.69%), and others (2, 3.85%). Respiratory Infection rate post high flow, tracheal intubation, and tracheotomy were 12.90% (4/31), 30.43% (7/23), and 92.31% (12/13) respectively. Secondary infections would lead to lower discharge rate and higher mortality rate. Conclusion Our study originally illustrated secondary infection proportion in severe and critical COVID-19 patients. Culture accompanied with metagenomics sequencing increased pathogen diagnostic rate. Secondary infections risks increased after receiving invasive respiratory ventilations and intravascular devices, and would lead to a lower discharge rate and a higher mortality rate.


Assuntos
Bacteriemia/patologia , Infecções Bacterianas/patologia , Infecções por Coronavirus/patologia , Fungemia/patologia , Micoses/patologia , Infecções Oportunistas/patologia , Pneumonia Viral/patologia , Infecções Respiratórias/patologia , Infecções Urinárias/patologia , Idoso , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Bacteriemia/virologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Infecções Bacterianas/virologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Estado Terminal , Feminino , Fungemia/microbiologia , Fungemia/mortalidade , Fungemia/virologia , Fungos/patogenicidade , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Positivas/patogenicidade , Humanos , Unidades de Terapia Intensiva , Pulmão/microbiologia , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Micoses/mortalidade , Micoses/virologia , Infecções Oportunistas/microbiologia , Infecções Oportunistas/mortalidade , Infecções Oportunistas/virologia , Pandemias , Pneumonia Viral/microbiologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Respiração Artificial/efeitos adversos , Infecções Respiratórias/microbiologia , Infecções Respiratórias/mortalidade , Infecções Respiratórias/virologia , Estudos Retrospectivos , Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Infecções Urinárias/microbiologia , Infecções Urinárias/mortalidade , Infecções Urinárias/virologia
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