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1.
Nat Commun ; 10(1): 4644, 2019 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604911

RESUMO

In mammalian cells, the internal and external leaflets of the plasma membrane (PM) possess different phospholipids. Phosphatidylserine (PS) is normally confined to the inner (cytoplasmic) membrane leaflet. Here we report that the adhesin CPn0473 of the human pathogenic bacterium Chlamydia pneumoniae (Cpn) binds to the PM of human cells and induces PS externalization but unexpectedly not apoptosis. PS externalization is increased in human cells exposed to infectious Cpn cells expressing increased CPn0473 and reduced in exposure to Cpn expressing decreased CPn0473. CPn0473 binds specifically to synthetic membranes carrying PS and stimulates pore formation. Asymmetric giant unilamellar vesicles (GUVs) in which PS is restricted to the inner leaflet reveal that CPn0473 induces PS externalization in the absence of other proteins. Thus our identification of CPn0473 as a bacterial PS translocator capable of specific and apoptosis-independent PS externalization during infection extends the spectrum of mechanisms intracellular pathogens use to enter host cells.


Assuntos
Adesinas Bacterianas/fisiologia , Chlamydophila pneumoniae/fisiologia , Fosfatidilserinas/metabolismo , Adesinas Bacterianas/metabolismo , Interações entre Hospedeiro e Microrganismos , Humanos , Lipídeos de Membrana/química , Lipídeos de Membrana/metabolismo , Proteínas de Transferência de Fosfolipídeos/metabolismo
2.
Vet Pathol ; 56(5): 789-793, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31221032

RESUMO

Chlamydia pneumoniae is a ubiquitous pathogen causing disease in humans, mammals, birds, reptiles, and amphibians. Since 2012, C. pneumoniae infection has caused neurologic disease and mortality in a breeding colony of endangered Houston toads (Anaxyrus houstonensis) at the Houston Zoo. The purpose of this report is to present the histopathologic and ultrastructural characteristics of C. pneumoniae infection in Houston toads. Fourteen cases were evaluated by histopathology and 1 case was evaluated by electron microscopy. The major histopathologic finding was necrotizing and histiocytic polioencephalomyelitis and ganglionitis. Bacteria formed intracytoplasmic inclusions within neurons but frequently extended into the surrounding tissue from necrotic cells. Ultrastructural evaluation showed the bacteria formed reticulate and elementary bodies characteristic of Chlamydia spp.


Assuntos
Bufonidae/microbiologia , Infecções por Chlamydophila/veterinária , Chlamydophila pneumoniae , Encefalomielite/veterinária , Animais , Animais de Zoológico , Infecções por Chlamydophila/microbiologia , Encefalomielite/microbiologia
3.
Mediators Inflamm ; 2019: 4742634, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236064

RESUMO

Chlamydia pneumoniae (Cpn) infection causes multiple acute and chronic human diseases. The role of DCs in host defense against Cpn infection has been well documented. The same is true for invariant natural killer T (iNKT) cells and NK cells, but the interaction among cells is largely unknown. In this study, we investigated the influence and mechanism of iNKT cell on the differentiation and function of NK cell in Cpn lung infection and the role played by DCs in this process. We found that expansion of IFN-γ-producing NK cells quickly happened after the infection, but this response was altered in iNKT knockout (KO) mice. The expression of activation markers and the production of IFN-γ by different NK subsets were significantly lower in KO mice than wild-type (WT) mice. Using in vitro DC-NK coculture and in vivo adoptive transfer approaches, we further examined the role of DCs in iNKT-mediated modulation of NK cell function. We found that NK cells expressed lower levels of activation markers and produced less IFN-γ when they were cocultured with DCs from KO mice than WT mice. More importantly, we found that the adoptive transfer of DCs from the KO mice induced less NK cell activation and IFN-γ production. The results provided evidence on the modulating effect of iNKT cell on NK cell function, particularly the critical role of DCs in this modulation process. The finding suggests the complexity of cellular interactions in Cpn lung infection, which should be considered in designing preventive and therapeutic approaches for diseases and infections.


Assuntos
Infecções por Chlamydophila/imunologia , Chlamydophila pneumoniae/patogenicidade , Células Dendríticas/metabolismo , Células Matadoras Naturais/metabolismo , Pneumopatias/imunologia , Pneumopatias/microbiologia , Animais , Feminino , Interferon gama/metabolismo , Pneumopatias/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células T Matadoras Naturais/metabolismo , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-31249813

RESUMO

Chlamydia trachomatis infections are the most prevalent sexually transmitted infections with potentially debilitating sequelae, such as infertility. Mouse models are generally used for vaccine development, to study the immune response and histopathology associated with Chlamydia infection. An important question regarding murine models is the in vivo identification of murine host genes responsible for the elimination of the murine and human Chlamydia strains. RNA sequencing of the Chlamydia muridarum infected BALB/c lung transcriptome revealed that several genes with direct antichlamydial functions were induced at the tissue level, including the already described and novel members of the murine interferon-inducible GTPase family, the CXCL chemokines CXCL9, CXCL11, immunoresponsive gene 1, nitric oxide synthase-2 (iNOS), and lipocalin-2. Indoleamine 2,3-dioxygenase 1-2 (IDO1-2) previously described potent antichlamydial host enzymes were also highly expressed in the infected murine lungs. This finding was novel, since IDO was considered as a unique human antichlamydial defense gene. Besides a lower level of epithelial cell positivity, immunohistochemistry showed that IDO1-2 proteins were expressed prominently in macrophages. Detection of the tryptophan degradation product kynurenine and the impact of IDO inhibition on Chlamydia muridarum growth proved that the IDO1-2 proteins were functionally active. IDO1-2 activity also increased in Chlamydia muridarum infected C57BL/6 lung tissues, indicating that this phenomenon is not mouse strain specific. Our study shows that the murine antichlamydial response includes a variety of highly up-regulated defense genes in vivo. Among these genes the antichlamydial effectors IDO1-2 were identified. The potential impact of murine IDO1-2 expression on Chlamydia propagation needs further investigation.


Assuntos
Infecções por Chlamydia/metabolismo , Chlamydia muridarum/efeitos dos fármacos , Chlamydia muridarum/metabolismo , Chlamydophila pneumoniae/efeitos dos fármacos , Chlamydophila pneumoniae/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/farmacologia , Pulmão/metabolismo , Animais , Quimiocina CXCL11/genética , Quimiocina CXCL11/metabolismo , Quimiocina CXCL9/genética , Quimiocina CXCL9/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Infecções por Chlamydia/genética , Infecções por Chlamydia/microbiologia , Infecções por Chlamydia/patologia , Modelos Animais de Doenças , Inibidores Enzimáticos/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Expressão Gênica , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/efeitos dos fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Cinurenina , Lipocalina-2/genética , Lipocalina-2/metabolismo , Pulmão/patologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Mensageiro/metabolismo , Transcriptoma , Triptofano/análogos & derivados , Triptofano/antagonistas & inibidores , Triptofano/metabolismo
5.
Vestn Otorinolaringol ; 84(1): 55-59, 2019.
Artigo em Russo | MEDLINE | ID: mdl-30938344

RESUMO

AIM: To study the characteristics of health state in family-members of ENT-patients with identified Chlamydia infection. METHODS: We have examined 245 members of 87 families of otorhinolaryngological patients with verified (44 families) and without (44 families) Chlamydia infection. Laboratory methods of the research included the identification of the following types: Chlamydia trachomatis and Chlamydophila pneumoniae. Chlamydia diagnostics involved both direct immune fluorescence and immune enzyme analyses as well as polymerase chain reaction. Health state in ENT-patient family-members has been evaluated by the complex method based on the special questionnaire for every family-member aimed at determining the health category, the calculation of health average coefficient for each family member followed by the determination of family identity with some definite health category. RESULTS: in the families of otorhinolaryngological patients with verified Chlamydia infection there have been revealed considerably more family-members with acute and chronic pathology of different organs and systems associated with functional disorders. The health status of family members of ENT patients with respiratory Chlamydia was significantly worse than in families of patients with negative laboratory results for Chlamydia, which was manifested by a much smaller number of healthy family members and a large number of people with risk factors for health.


Assuntos
Infecções por Chlamydia , Chlamydophila pneumoniae , Chlamydia trachomatis , Família , Saúde da Família , Humanos , Fatores de Risco
6.
Nagoya J Med Sci ; 81(1): 151-158, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30962664

RESUMO

Recent epidemiological or immunopathological studies demonstrate the possible association between giant cell arteritis and infectious agents including Chlamydia pneumoniae. A 62-year-old Japanese man with type 1 diabetes mellitus developed biopsy-proven giant cell arteritis after acute upper respiratory infection. Serological examination indicated concurrent re-infection with C. pneumoniae. Clinical manifestations of the vasculitis subsided within a month without any immunosuppressive therapy, and no relapse was observed for the following 12 months. The natural history of this disease is unclear and spontaneous remission is rarely reported. The self-limiting nature of the infection could contribute to this phenomenon.


Assuntos
Anticorpos Antibacterianos/sangue , Chlamydophila pneumoniae/imunologia , Chlamydophila pneumoniae/patogenicidade , Arterite de Células Gigantes/sangue , Arterite de Células Gigantes/imunologia , Infecções Respiratórias/sangue , Anticorpos Antibacterianos/imunologia , Arterite de Células Gigantes/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Remissão Espontânea , Infecções Respiratórias/imunologia , Infecções Respiratórias/microbiologia
7.
Adv Exp Med Biol ; 1160: 65-71, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016635

RESUMO

This study seeks to determine the pathogens in respiratory specimens and blood serum obtained from children who present with community acquired pneumonia (CAP) diagnosed on the basis of clinical and radiological evidence. The study group consisted of 46 hospitalized children aged 1-11 years. The material for research consisted of pharyngeal swabs and samples of blood serum. One hundred and thirty eight pharyngeal swabs were examined for the presence of C. pneumoniae antigen, C. pneumoniae DNA, and for typical pathogens. C. pneumoniae DNA was detected in pharyngeal swabs with nested PCR. Classical microbiological culture was used for detection of typical bacteria. ELISA test were used for detection anti-C. pneumoniae and anti-M. pneumoniae antibodies in the serum. C. pneumoniae DNA was identified in 10.9% of children. Positive culture for typical pathogens was observed in 8.7% of children. Specific anti-C. pneumoniae IgM antibodies were found in 8.7% of children, and IgG and IgA antibodies in 1 child each. Specific anti-M. pneumoniae IgG antibodies were found in 13.1% of children and IgM antibodies in 1 child. We conclude that the underlying bacterial etiology of CAP is rather rarely conclusively confirmed in children. Nonetheless, determining the etiology of CAP is essential for the choice of treatment to optimize the use and effectiveness of antimicrobials and to avoid adverse effect. Due to considerable variations in the power of detection of the type of atypical bacteria causing CAP, the search for the optimum diagnostic methods continues.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia Bacteriana , Anticorpos Antibacterianos/sangue , Criança , Pré-Escolar , Infecções por Chlamydophila/diagnóstico , Chlamydophila pneumoniae/fisiologia , Infecções Comunitárias Adquiridas/microbiologia , Humanos , Lactente , Mycoplasma pneumoniae/fisiologia , Pneumonia Bacteriana/microbiologia , Pneumonia por Mycoplasma/diagnóstico , Reação em Cadeia da Polimerase
8.
BMC Neurosci ; 20(1): 6, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30786875

RESUMO

BACKGROUND: Epidemiologic studies strongly suggest that the pathophysiology of late-onset Alzheimer disease (AD) versus early-onset AD has environmental rather than genetic causes, thus revealing potentially novel therapeutic targets to limit disease progression. Several studies supporting the "pathogen hypothesis" of AD demonstrate a strong association between pathogens and the production of ß-amyloid, the pathologic hallmark of AD. Although the mechanism of pathogen-induced neurodegeneration of AD remains unclear, astrocytes, a key player of the CNS innate immune response and producer/metabolizer of ß-amyloid, have been implicated. We hypothesized that Chlamydia pneumoniae infection of human astrocytes alters the expression of the amyloid precursor protein (APP)-processing secretases, ADAM10, BACE1, and PSEN1, to promote ß-amyloid formation. Utilizing immunofluorescent microscopy, molecular, and biochemical approaches, these studies explore the role of an intracellular respiratory pathogen, Chlamydia pneumoniae, as an environmental trigger for AD pathology. Human astrocytoma cells in vitro were infected with Chlamydia pneumoniae over the course of 6-72 h. The gene and protein expression, as well as the enzymatic activity of non-amyloidogenic (ADAM10), and pro-amyloidogenic (BACE1 and PSEN1) secretases were qualitatively and quantitatively assessed. In addition, the formation of toxic amyloid products as an outcome of pro-amyloidogenic APP processing was evaluated through various modalities. RESULTS: Chlamydia pneumoniae infection of human astrocytoma cells promoted the transcriptional upregulation of numerous genes implicated in host neuroinflammation, lipid homeostasis, microtubule function, and APP processing. Relative to that of uninfected astrocytes, BACE1 and PSEN1 protein levels were enhanced by nearly twofold at 48-72 h post-Chlamydia pneumoniae infection. The processing of APP in Chlamydia pneumoniae-infected astrocytes favors the pro-amyloidogenic pathway, as demonstrated by an increase in enzymatic activity of BACE1, while that of ADAM10 was decreased. Fluorescence intensity of ß-amyloid and ELISA-quantified levels of soluble-APP by products revealed temporally similar increases, confirming a BACE1/PSEN1-mediated processing of APP. CONCLUSIONS: Our findings suggest that Chlamydia pneumoniae infection of human astrocytes promotes the pro-amyloidogenic pathway of APP processing through the upregulation of expression and activity of ß-secretase, upregulated expression of γ-secretase, and decreased activity of α-secretase. These effects of astrocyte infection provide evidence for a direct link between Chlamydia pneumoniae and AD pathology.


Assuntos
Doença de Alzheimer/enzimologia , Peptídeos beta-Amiloides/metabolismo , Astrócitos/enzimologia , Infecções por Chlamydophila/enzimologia , Chlamydophila pneumoniae , Proteína ADAM10/metabolismo , Doença de Alzheimer/imunologia , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Astrócitos/imunologia , Astrócitos/patologia , Linhagem Celular Tumoral , Infecções por Chlamydophila/imunologia , Infecções por Chlamydophila/patologia , Expressão Gênica , Humanos , Inflamação/enzimologia , Inflamação/patologia , Proteínas de Membrana/metabolismo , Presenilina-1/metabolismo
9.
Front Immunol ; 10: 87, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804931

RESUMO

Atherosclerosis is a progressive disease characterized by chronic inflammation of the arterial walls, associated with genetic and infectious factors. The present study investigated the involvement of Chlamydia trachomatis and Chlamydia pneumoniae infections and immunological markers (C-reactive protein, CRP, TNF-α, IL-6, IL-8, and IL-10) in the process of atherosclerosis. The evaluation included 159 patients for surgical revascularization (CAD) and 71 patients for surgical heart valve disease (HVD) at three hospitals in Belém, Brazil. The control group (CG) comprised 300 healthy individuals. Blood samples collected before surgery were used for antibodies detection (enzyme immunoassay), CRP (immunoturbidimetry) and IL-6 levels (enzyme immunoassay). Tissue fragments (atheroma plaque, heart valve and ascending aorta) were collected during surgery and subjected to qPCR for detection of bacterial DNA. Promoter region polymorphisms of each marker and relative quantification of TNF-α, IL-8, and IL-10 gene expression were performed. Demography and social information were similar to the general population involved with both diseases. Antibody prevalence to C. trachomatis was 30.6, 20.3, and 36.7% (in the CAD, HVD, and CG, respectively) and to C. pneumoniae was 83.6, 84.5, and 80.3% (in the CAD, HVD, and CG, respectively). C. trachomatis cryptic plasmid DNA was detected in 7.4% of the samples. Frequency of IL6-174G>C polymorphism was higher in CAD and HVD than in CG regardless of previous exposure to Chlamydia. Previous C. trachomatis infection showed involvement in HVD and CAD. Significant association between disease and previous C. pneumoniae infection was found only among HVD. GG genotype of IL6-174G>C is apparently a risk factor for heart disease, whereas AT genotype of IL8-251A>T was mainly involved in valvulopathies, including patients with prior exposure to C. pneumoniae.


Assuntos
Aterosclerose/microbiologia , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis/fisiologia , Chlamydophila pneumoniae/fisiologia , Doenças das Valvas Cardíacas/microbiologia , Interleucina-6/genética , Interleucina-8/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Aterosclerose/epidemiologia , Aterosclerose/imunologia , Brasil/epidemiologia , Proteína C-Reativa/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Doenças das Valvas Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/imunologia , Humanos , Interleucina-10/genética , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Prevalência , Regiões Promotoras Genéticas/genética , Risco , Fator de Necrose Tumoral alfa/genética , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-30713347

RESUMO

Background: Atypical pathogen infections played an important role in community-acquired pneumonia (CAP) in children. Pathogen-specific clinical symptoms are often lacking, and it is difficult to detect atypical pathogens by culture methods. The use of multiplex polymerase chain reaction (PCR) methods enables testing for many pathogens simultaneously in a single analysis. Aim: To determine the role of atypical pathogens in children hospitalized with CAP. Patients and methods: This cross-sectional study was conducted throughout a 2-year period from August 2015 to September 2017. It included 400 Egyptian children hospitalized with clinical diagnosis of CAP at a tertiary hospital in Cairo, Egypt. Sputum samples were collected from lower respiratory tract of all enrolled patients by mucus trap catheter for identification of Bordetella pertussis, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophilia by using multiplex real-time PCR. Results: Among the 400 CAP patients enrolled in this study, atypical pathogens were detected in 12/400 (3%) patients. Bordetella pertussis was detected in 2% of cases, and it was responsible for CAP in 8/104 (7.69%) infants in the age stratum ≤ 4 months; compared with pertussis-negative cases, pertussis-positive cases were younger and incompletely vaccinated (P values were 0.001 and 0.007, respectively). Mycoplasma pneumoniae was detected in 1% of cases, all were among the age stratum > 4 months ≤ 59 months in 4/272 (1.47%) children. Conclusion: In early infancy, Bordetella pertussis causes a significant proportion of hospitalized CAP cases; all were ≤ 4 months old and incompletely vaccinated. This finding could suggest the role of maternal immunization in developing countries.


Assuntos
Bordetella pertussis/isolamento & purificação , Reação em Cadeia da Polimerase Multiplex/métodos , Pneumonia Bacteriana/diagnóstico , Criança , Pré-Escolar , Chlamydophila pneumoniae/isolamento & purificação , Infecções Comunitárias Adquiridas , Estudos Transversais , Egito/epidemiologia , Feminino , Humanos , Lactente , Legionella pneumophila/isolamento & purificação , Masculino , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia Bacteriana/microbiologia
11.
APMIS ; 127(3): 131-138, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30746791

RESUMO

Obligate intracellular bacterium Chlamydia pneumoniae causes respiratory tract infections such as community-acquired pneumonia. During infection, C. pneumoniae induces inflammatory responses in host cells and the oxygen concentration at the infection sites subsequently decreases. Because hypoxic conditions influence further inflammatory responses and reduced antibacterial effects, this may exacerbate the C. pneumoniae infection. Here, we show inflammatory responses and drug sensitivity in C. pneumoniae-infected cells under hypoxic conditions. First, we confirmed the enhanced growth of C. pneumoniae under hypoxia, which indicates that the hypoxic condition we used could adequately reproduce past reports. We then demonstrated a significant increase in production of the pro-inflammatory cytokine Interleukin 8 (IL-8) in C. pneumoniae-infected cells under hypoxic conditions. Furthermore, hypoxia decreased the antibacterial effects of azithromycin against C. pneumoniae compared with normoxic conditions. Together, our data suggest that inflammatory responses and drug sensitivity may have been underestimated in C. pneumoniae infection in previous studies. Thus, to accurately understand the Chlamydia infection, it may be necessary to perform in vitro experiments under hypoxic conditions.


Assuntos
Azitromicina/farmacologia , Hipóxia Celular/imunologia , Infecções por Chlamydophila , Chlamydophila pneumoniae/efeitos dos fármacos , Chlamydophila pneumoniae/fisiologia , Interações Hospedeiro-Patógeno , Interleucina-8/metabolismo , Antibacterianos/farmacologia , Linhagem Celular , Infecções por Chlamydophila/imunologia , Infecções por Chlamydophila/microbiologia , Chlamydophila pneumoniae/crescimento & desenvolvimento , Farmacorresistência Bacteriana/fisiologia , Humanos , Testes de Sensibilidade Microbiana
12.
BMC Infect Dis ; 19(1): 75, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30665366

RESUMO

BACKGROUND: Acute respiratory infections (ARIs) represent an important cause of morbidity and mortality in children, remaining a major public health concern, especially affecting children under 5 years old from low-income countries. Unfortunately, information regarding their epidemiology is still limited in Peru. METHODS: A secondary data analysis was performed from a previous cross-sectional study conducted in children with a probable diagnosis of Pertussis from January 2010 to July 2012. All samples were analyzed via Polymerase Chain Reaction (PCR) for the following etiologies: Influenza-A, Influenza-B, RSV-A, RSV-B, Adenovirus, Parainfluenza 1 virus, Parainfluenza 2 virus, Parainfluenza 3 virus, Mycoplasma pneumoniae and Chlamydia pneumoniae. RESULTS: A total of 288 patients were included. The most common pathogen isolated was Adenovirus (49%), followed by Bordetella pertussis (41%) from our previous investigation, the most prevelant microorganisms were Mycoplasma pneumonia (26%) and Influenza-B (19.8%). Coinfections were reported in 58% of samples and the most common association was found between B. pertussis and Adenovirus (12.2%). CONCLUSIONS: There was a high prevalence of Adenovirus, Mycoplasma pneumoniae and other etiologies in patients with a probable diagnosis of pertussis. Despite the presence of persistent cough lasting at least two weeks and other clinical characteristics highly suspicious of pertussis, secondary etiologies should be considered in children under 5 years-old in order to give a proper treatment.


Assuntos
Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Coqueluche/etiologia , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/etiologia , Bordetella pertussis/genética , Bordetella pertussis/isolamento & purificação , Pré-Escolar , Infecções por Chlamydophila/epidemiologia , Infecções por Chlamydophila/etiologia , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/isolamento & purificação , Tosse/microbiologia , Estudos Transversais , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Influenza Humana/epidemiologia , Influenza Humana/etiologia , Masculino , Mycoplasma pneumoniae/isolamento & purificação , Vírus da Parainfluenza 3 Humana/genética , Vírus da Parainfluenza 3 Humana/isolamento & purificação , Peru/epidemiologia , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/microbiologia , Infecções Respiratórias/epidemiologia , Infecções por Respirovirus/epidemiologia , Infecções por Respirovirus/etiologia , Coqueluche/diagnóstico , Coqueluche/epidemiologia
13.
PLoS One ; 14(1): e0210403, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30629647

RESUMO

Chlamydia pneumoniae is one of the two major species of the Chlamydiaceae family that have a profound effect on human health. C. pneumoniae is linked to a number of severe acute and chronic diseases of the upper and lower respiratory tract including pneumonia, asthma, bronchitis and infection by the pathogen might play a role in lung cancer. Following adhesion, Chlamydiae secrete effector proteins into the host cytoplasm that modulate the actin cytoskeleton facilitating internalization and infection. Members of the conserved TarP protein family comprise such effector proteins that polymerize actin, and in the case of the C. trachomatis TarP protein, has been shown to play a critical role in pathogenesis. In a previous study, we demonstrated that, upon bacterial invasion, the C. pneumoniae TarP family member CPn0572 is secreted into the host cytoplasm and recruits and associates with actin via an actin-binding domain conserved in TarP proteins. We have now extended our analysis of CPn0572 and found that the CPn0572 actin binding and modulating capability is more complex. With the help of the fission yeast system, a second actin modulating domain was identified independent of the actin binding domain. Microscopic analysis of HEp-2 cells expressing different CPn0572 deletion variants mapped this domain to the C-terminal part of the protein as CPn0572536-755 binds F-actin in vitro and colocalizes with aberrantly thickened actin cables in vivo. Finally, microscopic and bioinformatic analysis revealed the existence of a vinculin binding sequence in CPn0572. Our findings contribute to the understanding of the function of the TarP family and underscore the existence of several actin binding domains and a vinculin binding site for host actin modulation.


Assuntos
Proteínas de Bactérias/fisiologia , Chlamydophila pneumoniae/patogenicidade , Vinculina/metabolismo , Actinas/metabolismo , Proteínas de Bactérias/química , Sítios de Ligação , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/metabolismo , Biologia Computacional , Citoesqueleto/metabolismo , Humanos , Domínios Proteicos , Análise de Sequência de Proteína
14.
PLoS One ; 14(1): e0210640, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30629683

RESUMO

Cardiovascular disease (CVD) is an important contributor to morbidity and mortality in American Indian communities. The Strong Heart Study (SHS) was initiated in response to the need for population based estimates of cardiovascular disease in American Indians. Previous studies within SHS have identified correlations between heart disease and deficiencies in mannose binding lectin (MBL), a motif recognition molecule of the innate immune system. MBL mediates the immune response to invading pathogens including Chlamydia pneumoniae (Cp), which has also been associated with the development and progression of CVD. However, a link between MBL2 genotype and Cp in contributing to heart disease has not been established. To address this, SHS collected baseline Cp antibody titers (IgA and IgG) and MBL2 genotypes for common functional variants from 553 individuals among twelve participating tribes. A single nucleotide polymorphism (SNP) in the promoter, designated X/Y, correlated significantly with increased Cp IgG titer levels, whereas another promoter SNP (H/L) did not significantly influence antibody levels to Cp. Two variants within exon 1 of MBL2, the A and B alleles, also displayed significant association with Cp antibody titers. Some MBL2 genotypes were absent from the population, suggesting linkage disequilibrium may be operating within the SHS cohort. Additional factors, such as increasing age and socioeconomic status, were also associated with increased Cp IgG antibody titers. This study demonstrates that MBL2 genotype associates with immune reactivity to C. pneumoniae in the SHS cohort. Thus, MBL2 may contribute to the progression of cardiovascular disease (CVD) among American Indians indirectly through pathogen interactions in addition to its previously defined roles.


Assuntos
Chlamydophila pneumoniae/metabolismo , Chlamydophila pneumoniae/patogenicidade , Lectina de Ligação a Manose/metabolismo , Idoso , Alelos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Estudos de Casos e Controles , Chlamydophila pneumoniae/genética , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Índios Norte-Americanos , Desequilíbrio de Ligação/genética , Masculino , Lectina de Ligação a Manose/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética
15.
Infection ; 47(3): 471-474, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30689160

RESUMO

PURPOSE: To assess the incidence of Mycoplasma pneumoniae and Chlamydia pneumoniae in the pathogenesis of hospital-acquired respiratory tract infections (RTIs) in critically ill patients. METHODS: This is a retrospective cohort study of all ICU-patients ≥ 18 years with RTI who underwent conventional culture techniques and PCR testing for both M. pneumoniae and C. pneumoniae from respiratory tract specimens (bronchoalveolar lavage or tracheobronchial aspirates) between January 2013 to May 2017 at the Jena University Hospital. RESULTS: In total, 314 patients were included in the analysis. Of these, 210 (66.9%) patients were diagnosed with HAP, 65 (20.7%) with VAP and 39 (12.4%) with VAT. Overall, 73 (30.7%) patients were on mechanical ventilation on the day of microbiological examination. PCR-testing for M. pneumoniae was positive in two patients (0.6%) and for C. pneumoniae in zero patients. CONCLUSIONS: Our study shows that the incidence of M. pneumoniae and C. pneumoniae in the pathogenesis of hospital-acquired RTIs in critically ill patients is negligible. The results support the recommendations of the guidelines not to perform empiric therapy covering these pathogens.


Assuntos
Infecção Hospitalar/epidemiologia , Infecções Respiratórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Chlamydophila pneumoniae/fisiologia , Estudos de Coortes , Estado Terminal , Infecção Hospitalar/microbiologia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Mycoplasma pneumoniae/fisiologia , Respiração Artificial , Infecções Respiratórias/microbiologia , Estudos Retrospectivos , Adulto Jovem
16.
Immunol Cell Biol ; 97(1): 85-91, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30051926

RESUMO

We have shown previously that intranasal vaccination with recombinant chlamydial protease-like activity factor (rCPAF: antigen) and interleukin-12 (IL-12) as an adjuvant induces robust protection against pathological consequences of female genital tract infection with Chlamydia muridarum, a closely related species and a rodent model for the human pathogen Chlamydia trachomatis. Another related species Chlamydia pneumoniae, a human respiratory pathogen, has been associated with exacerbation of atherosclerotic pathology. CPAF is highly conserved among Chlamydia spp. leading us to hypothesize that immunization with rCPAF with IL-12 will protect against high-fat diet (HFD) and C. pneumoniae-induced acceleration of atherosclerosis. rCPAF ± IL-12 immunization induced robust splenic antigen (Ag)-specific IFN-γ and TNF-α production and significantly elevated serum total anti-CPAF Ab, IgG2c, and IgG1 antibody levels compared to mock or IL-12 alone groups. The addition of IL-12 to rCPAF significantly elevated splenic Ag-specific IFN-γ production and IgG2c/IgG1 anti-CPAF antibody ratio. Following intranasal C. pneumoniae challenge and HFD feeding, rCPAF ± IL-12-immunized mice displayed significantly enhanced splenic IFN-γ, not TNF-α, response on days 6 and 9 after challenge, and significantly reduced lung chlamydial burden on day 9 post-challenge compared to mock- or IL-12-immunized mice. Importantly, rCPAF ± IL-12-immunized mice displayed significantly reduced atherosclerotic pathology in the aortas after C. pneumoniae challenge. Serum cholesterol levels were comparable between the groups suggesting that the observed differences in pathology were due to protective immunity against the infection. Together, these results confirm and extend our previous observations that CPAF is a promising candidate antigen for a multisubunit vaccine regimen to protect against Chlamydia-induced pathologies, including atherosclerosis.


Assuntos
Aterosclerose/imunologia , Infecções por Chlamydophila/prevenção & controle , Chlamydophila pneumoniae/imunologia , Endopeptidases/administração & dosagem , Interleucina-12/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Animais , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/imunologia , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Infecções por Chlamydophila/complicações , Endopeptidases/genética , Endopeptidases/imunologia , Imunogenicidade da Vacina , Interleucina-12/imunologia , Camundongos , Proteínas Recombinantes/imunologia
18.
Infect Dis Health ; 24(2): 67-74, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30541691

RESUMO

BACKGROUND: Chlamydia pneumoniae is a pathogen associated with human respiratory tract infection, its viable presence in atherosclerotic plaques is also assumed to play significant function in cardiac diseases. Our study's main objective is to evaluate Chlamydia pneumoniae sero-prevalence in Moroccan patients with cardiovascular diseases using and comparing two serological methods. METHODS: Two hundred eighteen patients were enrolled; serums were tested by microimmunofluorescence to explore the sero-prevalence. Simultaneously 74 serums were analyzed by both immunoblot and micro-immunofluorescence to evaluate recombinant proteins diagnosis value. RESULTS: MIF results revealed 81% male and 84.5% female positive cases. The comparative study among 74 patients showed 78% men and 89% women positive cases by immunoblot, whereas MIF showed respectively 80% and 72%, a significant concordance between these methods was revealed. However, this comparison showed also two types of discrepancies, which may be related to difficulties in antigens detection by micro-immunofluorescence resulting from their structure complexity, or the antibodies reactivity with species' common antigens. CONCLUSIONS: The study revealed a high sero-prevalence of Chlamydia pneumoniae in the studied population, a big interest of recombinant protein was also revealed in the diagnosis accuracy. We suggest therefore using immunoblot for diagnosis confirmation because it provides additional useful information.


Assuntos
Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/sangue , Doenças Cardiovasculares/microbiologia , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/complicações , Infecções por Chlamydia/complicações , Chlamydophila pneumoniae , Feminino , Imunofluorescência , Humanos , Immunoblotting , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Estudos Soroepidemiológicos , Testes Sorológicos/normas
19.
J Int Med Res ; 47(2): 635-640, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30392431

RESUMO

OBJECTIVE: Osteoarthritis (OA) is a common cause of disability affecting millions of people of all ages worldwide. The pathogenesis involves an inflammatory component, but the cause of the inflammation remains incompletely understood. The intracellular bacteria Chlamydia trachomatis and C. pneumoniae have been demonstrated in patients with reactive arthritis. Both of these microorganisms can cause chronic and persistent infections, with C. trachomatis being the most common cause of reactive arthritis. This study was performed to investigate the presence of C. pneumoniae in a large number of patients with primary OA. METHODS: The study included 75 patients who underwent total knee arthroplasty. During surgery, a synovial biopsy was performed and synovial fluid drawn. Real-time polymerase chain reaction (PCR) of C. pneumoniae was run on all patients, and real-time PCR of bacterial 16S rDNA was conducted on 30 of the 75 patients to screen for the presence of other bacteria. RESULTS: Real-time PCR showed no evidence of the presence of C. pneumoniae in the patients' specimens, nor were other bacteria detected. CONCLUSIONS: Although an inflammatory component is part of the pathogenesis of OA, we found no evidence indicating that C. pneumoniae is a stimulator of that inflammation.


Assuntos
Infecções por Chlamydophila/complicações , Chlamydophila pneumoniae/isolamento & purificação , Osteoartrite/microbiologia , Líquido Sinovial/microbiologia , Membrana Sinovial/microbiologia , Sinovite/diagnóstico , Idoso , Artroplastia , Infecções por Chlamydophila/microbiologia , DNA Bacteriano/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/genética , Osteoartrite/cirurgia , Reação em Cadeia da Polimerase , Prognóstico , RNA Ribossômico 16S/genética , Sinovite/genética , Sinovite/microbiologia
20.
Free Radic Biol Med ; 131: 309-317, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30578916

RESUMO

Redox signaling has been established as an essential component of inflammatory responses, and redox active compounds are of interest as potential immunomodulatory agents. Dibenzocyclooctadiene lignans isolated from Schisandra chinensis, a medicinal plant with widespread use in oriental medicine, have been implicated to possess immunomodulatory properties but their effects on the human innate immune system cells have not been described. In this contribution, data are presented on the impact of schisandrin, schisandrin B and schisandrin C on human monocytic cell redox status, as well as their impact on dendritic cell maturation and T cell activation capacity and cytokine production. In THP-1 cells, levels of intracellular reactive oxygen species (ROS) were elevated after 1 h exposure to schisandrin. Schisandrin B and schisandrin C decreased cellular glutathione pools, which is a phenotype previously reported to promote anti-inflammatory functions. Treatment of human primary monocytes with the lignans during their maturation to dendritic cells did not have any effect on the appearance of surface markers HLA-DR and CD86 but schisandrin B and schisandrin C suppressed the secretion of cytokines interleukin (IL)-6, IL-10 and IL-12 by the mature dendritic cells. Dendritic cells maturated in presence of schisandrin C were further cocultured with naïve CD4+ T cells, resulting in reduced IL-12 production. In THP-1 cells, schisandrin B and schisandrin C reduced the IL-6 and IL-12 production triggered by E. coli lipopolysaccharide and IL-12 production induced by an infection with Chlamydia pneumoniae. In conclusion, the studied lignans act as immunomodulatory agents by altering the cytokine secretion, but do not interfere with dendritic cell maturation. And the observed effects may be associated with the ability of the lignans to alter cellular redox status.


Assuntos
Ciclo-Octanos/farmacologia , Células Dendríticas/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Lignanas/farmacologia , Compostos Policíclicos/farmacologia , Linfócitos T/efeitos dos fármacos , Antígeno B7-2/genética , Antígeno B7-2/imunologia , Chlamydophila pneumoniae/crescimento & desenvolvimento , Técnicas de Cocultura , Ciclo-Octanos/isolamento & purificação , Células Dendríticas/imunologia , Expressão Gênica/efeitos dos fármacos , Glutationa/imunologia , Glutationa/metabolismo , Antígenos HLA-DR/genética , Antígenos HLA-DR/imunologia , Humanos , Fatores Imunológicos/isolamento & purificação , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Lignanas/isolamento & purificação , Lipopolissacarídeos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Compostos Policíclicos/isolamento & purificação , Cultura Primária de Células , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Schisandra/química , Linfócitos T/imunologia , Linfócitos T/microbiologia , Células THP-1
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