RESUMO
Chlamydia pneumoniae is a type of pathogenic gram-negative bacteria that causes various respiratory tract infections including asthma. Chlamydia species infect humans and cause respiratory infection by rupturing the lining of the respiratory which includes the throat, lungs and windpipe. Meanwhile, the function of interleukin-4 (IL-4) in Ch. pneumoniae respiratory infection and its association with the development of airway hyperresponsiveness (AHR) in adulthood and causing allergic airway disease (AAD) are not understood properly. We therefore investigated the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. In this study, Ch. pneumonia strain was propagated and cultured in HEp-2 cells according to standard protocol and infant C57BL/6 mice around 3-4 weeks old were infected to study the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. We observed that IL-4 is linked with Chlamydia respiratory infection and its absence lowers respiratory infection. IL-4R α2 is also responsible for controlling the IL-4 signaling pathway and averts the progression of infection and inflammation. Furthermore, the IL-4 signaling pathway also influences infection-induced AHR and aids in increasing AAD severity. STAT6 also promotes respiratory infection caused by Ch. pneumoniae and further enhanced its downstream process. Our study concluded that IL-4 is a potential target for preventing infection-induced AHR and severe asthma.
Assuntos
Infecções por Chlamydia/metabolismo , Interleucina-4/metabolismo , Hipersensibilidade Respiratória/metabolismo , Infecções Respiratórias/metabolismo , Animais , Infecções por Chlamydia/complicações , Infecções por Chlamydia/microbiologia , Chlamydophila pneumoniae/patogenicidade , Pulmão/metabolismo , Pulmão/patologia , Ativação de Macrófagos/genética , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/patologia , Infecções Respiratórias/etiologia , Infecções Respiratórias/microbiologia , Transdução de SinaisRESUMO
Community-acquired pneumonia (CAP) is a common illness that can lead to mortality. ß-lactams are ineffective against atypical pathogen including Mycoplasma pneumoniae. We used molecular examinations to develop a decision tree to predict atypical pathogens with CAP and to examine the prevalence of macrolide resistance in Mycoplasma pneumoniae. We conducted a prospective observational study of patients aged ≥ 18 years who had fever and respiratory symptoms and were diagnosed with CAP in one of two community hospitals between December 2016 and October 2018. We assessed combinations of clinical variables that best predicted atypical pathogens with CAP by classification and regression tree (CART) analysis. Pneumonia was defined as respiratory symptoms and new infiltration recognized on chest X-ray or chest computed tomography. We analyzed 47 patients (21 females, 44.7%, mean age: 47.6 years). Atypical pathogens were detected in 15 patients (31.9%; 12 Mycoplasma pneumoniae, 3 Chlamydophila pneumoniae). Ten patients carried macrolide resistant Mycoplasma pneumoniae (macrolide resistant rate 83.3%). CART analysis suggested that factors associated with presence of atypical pathogens were absence of crackles, age < 45 years, and LD ≥ 183 U/L (sensitivity 86.7% [59.5, 98.3], specificity 96.9% [83.8, 99.9]). ur simple clinical decision rules can be used to identify primary care patients with CAP that are at risk for atypical pathogens. Further research is needed to validate its usefulness in various populations.Trial registration Clinical Trial (UMIN trial ID: UMIN000035346).
Assuntos
Pneumonia/etiologia , Infecções Respiratórias/complicações , Adulto , Idoso , Antibacterianos/uso terapêutico , Área Sob a Curva , Chlamydophila pneumoniae/efeitos dos fármacos , Chlamydophila pneumoniae/patogenicidade , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Estudos Epidemiológicos , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/patogenicidade , Pneumonia/epidemiologia , Pneumonia/microbiologia , Reação em Cadeia da Polimerase/métodos , Prevalência , Estudos Prospectivos , Curva ROC , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologiaRESUMO
BACKGROUND: Chlamydia pneumoniae (Cp) is an obligate intracellular human respiratory pathogen producing persisting lung infection with a plausible link to asthma pathogenesis. The population attributable risk of potentially treatable Cp infection in asthma has not been reported. METHODS: The author searched from 2000 to 2020 inclusive for previously un-reviewed and new cross sectional and prospective controlled studies of Cp biomarkers and chronic asthma in both children and adults. Qualitative descriptive results and quantitative estimates of population attributable risk for selected biomarkers (specific IgG, IgA and IgE) are presented. FINDINGS: No large, long-term prospective population-based studies of Cp infection and asthma were identified. About half of case-control studies reported one or more significant associations of Cp biomarkers and chronic asthma. Heterogeneity of results by age group (pediatric v adult asthma), severity category (severe/uncontrolled, moderate/partly controlled, mild/controlled) and antibody isotype (specific IgG, IgA, IgE) were suggested by the qualitative results and confirmed by meta-analyses. The population attributable risks for Cp-specific IgG and IgA were nul in children and were 6% (95% confidence interval 2%-10%, p = 0.002) and 13% (9%-18%, p<0.00001) respectively in adults. In contrast to the nul or small population attributable risks for Cp-specific IgG and IgA, the population attributable risk for C. pneumoniae-specific IgE (children and adults combined) was 47% (39%-55%, p<0.00001). In the subset of studies that reported on asthma severity categories, Cp biomarkers were positively and significantly (P<0.00001) associated with asthma severity. INTERPRETATION: C. pneumoniae-specific IgE is strongly associated with asthma and asthma severity, suggesting a possible mechanism linking chronic Cp infection with asthma in a subset of individuals with asthma. Infection biomarkers should be included in future macrolide treatment trials for severe and uncontrolled asthma.
Assuntos
Asma/etiologia , Asma/microbiologia , Chlamydophila pneumoniae/patogenicidade , Asma/fisiopatologia , Biomarcadores , Estudos de Casos e Controles , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydophila/complicações , Infecções por Chlamydophila/epidemiologia , Doença Crônica , Estudos Transversais , Humanos , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Fatores de RiscoAssuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/microbiologia , Modelos Biológicos , Placa Amiloide/microbiologia , Adulto , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Animais , Borrelia burgdorferi/patogenicidade , Chlamydophila pneumoniae/patogenicidade , Predisposição Genética para Doença , Sistema Glinfático , Humanos , Imunidade Inata , Inflamação , Proteínas de Membrana/genética , Camundongos , Pessoa de Meia-Idade , Organoides/metabolismo , Organoides/patologia , Placa Amiloide/tratamento farmacológico , Placa Amiloide/genética , Placa Amiloide/metabolismo , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Porphyromonas gingivalis/patogenicidade , Proteínas de Ligação a RNA/genética , Simplexvirus/efeitos dos fármacos , Simplexvirus/patogenicidade , Tauopatias/metabolismo , Valaciclovir/uso terapêutico , Proteínas tau/metabolismoRESUMO
BACKGROUND: Acute respiratory infections are a common disease in children with high mortality and morbidity. Multiple pathogens can cause acute respiratory infections. A 2-year survey of hospitalized children was conducted to understand the epidemic situation, seasonal spread of pathogens and the improvement of clinical diagnosis, treatment and prevention of disease in Huzhou, China. METHODS: From September 2017 to August 2019, 3121 nasopharyngeal swabs from hospitalized children with acute respiratory infections were collected, and real-time PCR was used to detect various pathogens. Then, pathogen profiles, frequency and seasonality were analyzed. RESULTS: Of the 3121 specimens, 14.45% (451/3121) were positive for at least one pathogen. Of the single-pathogen infections, RSV (45.61%, 182/399) was the most frequent pathogen, followed by PIVs (14.79%, 59/399), ADV (14.54%, 58/399), MP (10.78%, 43/399), and IAV (5.26%, 21/399). Of the 52 coinfections, RSV + PIVs viruses were predominantly identified and accounted for 40.38% (21/52) of cases. RSV was the most frequent pathogen in all four groups. The highest positive rate of the pathogens occurred in the winter (21.26%), followed by autumn (14.98%), the summer (14.11%) and the spring (12.25%). CONCLUSION: Viruses are the main pathogens in hospitalized children with acute respiratory infections in Huzhou city, Zhejiang Province, China. Among the pathogens, RSV had the highest detection rate, and MP is also a common pathogen among children with acute respiratory infections. This study provided a better understanding of the distribution of pathogens in children of different ages and seasons, which is conducive to the development of more reasonable treatment strategies and prevention and control measures.
Assuntos
Infecções por Chlamydophila/epidemiologia , Infecções por Vírus de DNA/epidemiologia , Vírus de DNA/patogenicidade , Pneumonia por Mycoplasma/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Doença Aguda/epidemiologia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/patogenicidade , Coinfecção/microbiologia , Coinfecção/virologia , Vírus de DNA/genética , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/patogenicidade , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sinciciais Respiratórios/genética , Vírus Sinciciais Respiratórios/patogenicidade , Infecções Respiratórias/epidemiologia , Estações do AnoRESUMO
BACKGROUND: Molecular diagnostic methods have recently gained widespread use, and consequently, the importance of viral pathogens in community-acquired pneumonia (CAP) has undergone re-evaluation. Under these circumstances, the role of Chlamydophila pneumoniae as a pathogen that causes CAP also needs to be reviewed. METHODS: We reviewed articles that contained data on the frequency of identification of C. pneumoniae pneumonia as a causative pathogen for CAP. The articles were identified by performing a search in PubMed with the keywords "community-acquired pneumonia" and "pathogen". RESULTS: Sixty-three articles were identified. The reviewed articles demonstrated that the rates of identification of C. pneumoniae as the causative pathogen for CAP were significantly lower in assessments based on polymerase chain reaction (PCR) methods than in those based on serological methods. In some studies, it was possible to compare both serological and PCR methods directly using the same set of samples. CONCLUSIONS: The use of PCR methods, including multiplex PCR assays, has revealed that C. pneumoniae may play a limited role as a pathogen for CAP.
Assuntos
Infecções por Chlamydophila , Chlamydophila pneumoniae/isolamento & purificação , Chlamydophila pneumoniae/patogenicidade , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/microbiologia , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase Multiplex/métodos , Testes Sorológicos/métodosRESUMO
BACKGROUND: Chlamydia pneumoniae is an obligate intracellular bacterium that causes respiratory infection. There may exist an association between C. pneumoniae, asthma, and production of immunoglobulin (Ig) E responses in vitro. Interleukin (IL-4) is required for IgE production. OBJECTIVE: We previously demonstrated that doxycycline suppresses C. pneumoniae-induced production of IgE and IL-4 responses in peripheral blood mononuclear cells (PBMC) from asthmatic subjects. Whereas macrolides have anti-chlamydial activity, their effect on in vitro anti-inflammatory (IgE) and IL-4 responses to C. pneumoniae have not been studied. METHODS: PBMC from IgE- adult atopic subjects (N = 5) were infected +/- C. pneumoniae BAL69, +/- azithromycin (0.1, 1.0 ug/mL) for 10 days. IL-4 and IgE levels were determined in supernatants by ELISA. IL-4 and IgE were detected in supernatants of PBMC (day 10). RESULTS: When azithromycin (0.1, 1.0 ug/ml) was added, IL-4 levels decreased. At low dose, IgE levels increased and at high dose, IgE levels decreased. When PBMC were infected with C. pneumoniae, both IL-4 and IgE levels decreased. Addition of azithromycin (0.1, 1.0 ug/mL) decreased IL-4 levels and had no effect on IgE levels. CONCLUSIONS: These findings indicate that azithromycin decreases IL-4 responses but has a bimodal effect on IgE responses in PBMC from atopic patients in vitro.
Assuntos
Azitromicina/farmacologia , Chlamydophila pneumoniae/imunologia , Imunoglobulina E/biossíntese , Interleucina-4/biossíntese , Idoso , Antibacterianos/farmacologia , Asma/complicações , Asma/tratamento farmacológico , Asma/imunologia , Infecções por Chlamydophila/complicações , Infecções por Chlamydophila/tratamento farmacológico , Infecções por Chlamydophila/imunologia , Chlamydophila pneumoniae/efeitos dos fármacos , Chlamydophila pneumoniae/patogenicidade , Feminino , Humanos , Hipersensibilidade Imediata/complicações , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/microbiologia , Imunoglobulina E/sangue , Técnicas In Vitro , Interleucina-4/sangue , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/complicações , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/imunologia , Adulto JovemRESUMO
Protective immune response to chlamydial infection is largely dependent on cell-mediated immune responses with IFN-γ production. Recent studies have shown the critical role of NK cells in bridging innate and adaptive immune responses. In this study, we investigated the effect of NK cells on T cell responses during Chlamydophila pneumoniae (Cpn) lung infection. The results showed that NK cells play a protective role in Cpn infection and influence T cell immunity largely though modulating dendritic cells (DCs) function. Specifically, we found that NK depletion significantly impaired type 1 T cell responses, but enhanced FOXP3+Treg cells and IL-10-producing CD4+T cells. The alteration of T cell responses was associated with more disease severity and higher chlamydial growth in the lung. Further analysis of DC phenotype and cytokine profile found that DCs from NK cell-depleted mice expressed lower levels of co-stimulatory molecules and produced higher levels of IL-10 than those from control IgG-treated mice. More importantly, the adoptive transfer of DCs from NK cell-depleted mice induced a much lower degree of type 1 T cell responses but a higher amount of FOXP3+ Treg cells and IL-10-producing CD4+T cells in the recipient mice than DCs from IgG-treated mice. In contrast to the strong protective effect observed in recipients of DCs from IgG-treated mice, the recipients of DCs from NK cell-depleted mice failed to be protected against Cpn infection. The data suggest that NK cells play a critical role in coordinating innate and adaptive immunity in Cpn lung infection by modulating the DC function to influence T cell responses.
Assuntos
Infecções por Chlamydophila/imunologia , Chlamydophila pneumoniae/imunologia , Células Matadoras Naturais/imunologia , Transferência Adotiva , Animais , Chlamydophila pneumoniae/metabolismo , Chlamydophila pneumoniae/patogenicidade , Citocinas/metabolismo , Células Dendríticas/imunologia , Imunidade Celular/imunologia , Células Matadoras Naturais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células T Matadoras Naturais/imunologia , Pneumonia Bacteriana/imunologiaRESUMO
BACKGROUND: Alzheimer's disease (AD) is a degenerative brain disease. A novel agent-based modelling framework was developed in NetLogo 3D to provide fundamental insights into the potential mechanisms by which a microbe (eg. Chlamydia pneumoniae) may play a role in late-onset AD. The objective of our initial model is to simulate one possible spatial and temporal pathway of bacterial propagation via the olfactory system, which may then lead to AD symptoms. The model maps the bacteria infecting cells from the nasal cavity and the olfactory epithelium, through the olfactory bulb and into the olfactory cortex and hippocampus regions of the brain. RESULTS: Based on the set of biological rules, simulated randomized infection by the microbe led to the formation of beta-amyloid (Aß) plaque and neurofibrillary (NF) tangles as well as caused immune responses. Our initial simulations demonstrated that breathing in C. pneumoniae can result in infection propagation and significant buildup of Aß plaque and NF tangles in the olfactory cortex and hippocampus. Our model also indicated how mucosal and neural immunity can play a significant role in the pathway considered. Lower immunities, correlated with elderly individuals, had quicker and more Aß plaque and NF tangle formation counts. In contrast, higher immunities, correlated with younger individuals, demonstrated little to no such formation. CONCLUSION: The modelling framework provides an organized visual representation of how AD progression may occur via the olfactory system to better understand disease pathogenesis. The model confirms current conclusions in available research but can be easily adjusted to match future evidence and be used by researchers for their own individual purposes. The goal of our initial model is to ultimately guide further hypothesis refinement and experimental testing to better understand the dynamic system interactions present in the etiology and pathogenesis of AD.
Assuntos
Doença de Alzheimer , Chlamydophila pneumoniae , Emaranhados Neurofibrilares , Bulbo Olfatório , Análise de Sistemas , Doença de Alzheimer/metabolismo , Doença de Alzheimer/microbiologia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Córtex Cerebral , Chlamydophila pneumoniae/patogenicidade , Humanos , Emaranhados Neurofibrilares/metabolismo , Bulbo Olfatório/metabolismo , Placa Amiloide/metabolismoRESUMO
Chlamydia pneumoniae is a spherical zoonotic pathogen with a diameter of â¼200 nm, which can lead to a wide range of acute and chronic diseases in human body. Early and reliable on-site detection of C. pneumoniae is the key step to control the spread of the pathogen. However, the lack of a current technology with advantages of rapidity, ultrasensitivity, and convenience limits the implementation of traditional techniques for on-site detection of C. pneumoniae. Herein, we developed a naked-eye counting of C. pneumoniae based on the light scattering properties of gold nanoparticle (GNP) under dark-field microscopy (termed "GNP-labeled dark-field counting strategy"). The recognition of single C. pneumoniae by anti-C. pneumoniae antibodies-functionalized GNP probes with size of 15 nm leads to the formation of wreath-like structure due to the strong scattered light resulted from hundreds of GNP probes binding on one C. pneumoniae under dark-field microscopy. Hundreds of GNP probes can bind to the surface of C. pneumoniae due to the high stability and specificity of the nucleic acid immuno-GNP probes, which generates by the hybridization of DNA-modified GNP with DNA-functionalized antibodies. The limit of detection (LOD) of the GNP-labeled dark-field counting strategy for C. pneumoniae detection in spiked samples or real samples is down to four C. pneumoniae per microliter, which is about 4 times more sensitive than that of quantitative polymerase chain reaction (qPCR). Together with the advantages of the strong light scattering characteristic of aggregated GNPs under dark-field microscopy and the specific identification of functionalized GNP probes, we can detect C. pneumoniae in less than 30 min using a cheap and portable microscope even if the sample contains only a few targets of interest and other species at high concentration. The GNP-labeled dark-field counting strategy meets the demands of rapid detection, low cost, easy to operate, and on-site detection, which paves the way for early and on-site detection of infectious pathogens.
Assuntos
Técnicas Biossensoriais/métodos , Pneumonia por Clamídia/diagnóstico , Chlamydophila pneumoniae/patogenicidade , Difusão Dinâmica da Luz/métodos , Ouro/química , Nanopartículas Metálicas/química , Humanos , Limite de DetecçãoRESUMO
Atherosclerotic vascular disease (ASVD) is a chronic process, with a progressive course over many years, but it can cause acute clinical events, including acute coronary syndromes (ACS), myocardial infarction (MI) and stroke. In addition to a series of typical risk factors for atherosclerosis, like hyperlipidemia, hypertension, smoking and obesity, emerging evidence suggests that atherosclerosis is a chronic inflammatory disease, suggesting that chronic infection plays an important role in the development of atherosclerosis. Toll-like receptors (TLRs) are the most characteristic members of pattern recognition receptors (PRRs), which play an important role in innate immune mechanism. TLRs play different roles in different stages of infection of atherosclerosis-related pathogens such as Chlamydia pneumoniae (C. pneumoniae), periodontal pathogens including Porphyromonas gingivalis (P. gingivalis), Helicobacter pylori (H. pylori) and human immunodeficiency virus (HIV). Overall, activation of TLR2 and 4 seems to have a profound impact on infection-related atherosclerosis. This article reviews the role of TLRs in the process of atherosclerosis after C. pneumoniae and other infections and the current status of treatment, with a view to providing a new direction and potential therapeutic targets for the study of ASVD.
Assuntos
Aterosclerose/genética , Infecções Bacterianas/genética , Infecções por HIV/genética , Receptores Toll-Like/genética , Aterosclerose/complicações , Aterosclerose/microbiologia , Aterosclerose/virologia , Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Chlamydophila pneumoniae/patogenicidade , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Helicobacter pylori/patogenicidade , Humanos , Porphyromonas gingivalis/patogenicidadeRESUMO
Chlamydia pneumonia (C.pn) is a common respiratory pathogen that is involved in human cardiovascular diseases and promotes the development of atherosclerosis in hyperlipidemic animal models. C.pn reportedly up-regulated lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in endothelial cells. Recently, the anti-atherosclerotic activity of peroxisome proliferator-activated receptor γ (PPARγ) has been documented. In the present study, we investigated the effect of C.pn on LOX-1 expression in human umbilical vein endothelial cells (HUVECs) and identified the involvement of the PPARγ signaling pathway therein. The results showed that C.pn increased the expression of LOX-1 in HUVECs in a dose- and time-dependent manner. C.pn-induced up-regulation of LOX-1 was mediated by ERK1/2, whereas p38 MAPK and JNK had no effect on this process. C.pn induced apoptosis, inhibited cell proliferation, and decreased the expression PPARγ in HUVECs. Additionally, LOX-1 activity and cell injury caused by C.pn through activation of ERK1/2 was completely inhibited by rosiglitazone, a PPARγ agonist. In conclusion, we inferred that activation of PPARγ in HUVECs suppressed C.pn-induced LOX-1 expression and cell damage by inhibiting ERK1/2 signaling.
Assuntos
Aterosclerose/genética , Doenças Cardiovasculares/genética , PPAR gama/genética , Receptores Depuradores Classe E/genética , Apoptose/genética , Aterosclerose/microbiologia , Aterosclerose/patologia , Doenças Cardiovasculares/microbiologia , Doenças Cardiovasculares/patologia , Proliferação de Células/genética , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/patogenicidade , Regulação da Expressão Gênica/genética , Células Endoteliais da Veia Umbilical Humana/microbiologia , Humanos , Sistema de Sinalização das MAP Quinases/genética , PPAR gama/agonistas , Rosiglitazona/farmacologia , Transdução de Sinais/efeitos dos fármacos , Veias Umbilicais/metabolismo , Veias Umbilicais/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
The obligate intracellular bacterium, Chlamydia pneumoniae, has been identified as a risk factor for several chronic inflammatory diseases in addition to respiratory tract infections. The dissemination of C. pneumoniae from respiratory tract to secondary sites of infection occurs via infected monocyte / macrophage line cells, in which C. pneumoniae can persist as an antibiotic-refractory phenotype. To allow more detailed studies on the epithelium-monocyte/macrophage transition of the infection, new in vitro bioassays are needed. To this end, a coculture system with human continuous cell lines was established. Respiratory epithelial HL cells were infected with C. pneumoniae and THP-1 monocytes were added into the cultures at 67 h post infection. After a 5 h coculture, THP-1 cells were collected with a biotinylated HLA antibody and streptavidin-coated magnetic beads and C. pneumoniae genome copy numbers in THP-1 determined by quantitative PCR. The assay was optimized for cell densities, incubation time, THP-1 separation technique and buffer composition, and its robustness was demonstrated by a Z' value of 0.6. The mitogen-activated protein kinase (MAPK) inhibitors: SP600125 (JNK inhibitor), SB203580 (p38 inhibitor) and FR180204 (ERK inhibitor) suppressed the transfer of C. pneumoniae from HL to THP-1 cells, making them suitable positive controls for the assay. Based on analysis of separate steps of the process, the MAPK inhibitors suppress the bacterial entry to THP-1 cells. The transfer of C. pneumoniae from epithelium to phagocytes represents a crucial step in the establishment of persistent infections by this pathogen, and the presented methods enables future studies to block this process by therapeutic means.
Assuntos
Infecções por Chlamydophila/patologia , Infecções por Chlamydophila/transmissão , Células Epiteliais/microbiologia , Macrófagos/microbiologia , Monócitos/microbiologia , Antracenos/farmacologia , Linhagem Celular , Chlamydophila pneumoniae/patogenicidade , Técnicas de Cocultura , Epitélio/microbiologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Humanos , Imidazóis/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Reação em Cadeia da Polimerase/métodos , Pirazóis , Piridazinas , Piridinas/farmacologia , Células THP-1 , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
Alzheimer's disease, the most common form of dementia, was first formally described in 1907 yet its etiology has remained elusive. Recent proposals that Aß peptide may be part of the brain immune response have revived longstanding contention about the possibility of causal relationships between brain pathogens and Alzheimer's disease. Research has focused on infectious pathogens that may colonize the brain such as herpes simplex type I. Some researchers have proposed the respiratory bacteria Chlamydia pneumoniae may also be implicated in Alzheimer's disease, however this remains controversial. This review aims to provide a balanced overview of the current evidence and its limitations and future approaches that may resolve controversies. We discuss the evidence from in vitro, animal and human studies proposed to implicate Chlamydia pneumoniae in Alzheimer's disease and other neurological conditions, the potential mechanisms by which the bacterium may contribute to pathogenesis and limitations of previous studies that may explain the inconsistencies in the literature.
Assuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/microbiologia , Chlamydophila pneumoniae/patogenicidade , Incerteza , Animais , Encéfalo/microbiologia , Infecções por Chlamydophila/complicações , Infecções por Chlamydophila/microbiologia , Humanos , Reprodutibilidade dos TestesRESUMO
Respiratory tract infections (RTIs) are severe acute infectious diseases, which require the timely and accurate identification of the pathogens involved so that the individual treatment plan can be selected, including optimized use of antibiotics. However, high throughput and ultrasensitive quantification of multiple nucleic acids is a challenge in a point of care testing (POCT) device. Methods: Herein, we developed a 2×3 microarray on a lateral flow strip with surface enhanced Raman scattering (SERS) nanotags encoding the nucleic acids of 11 common RTI pathogens. On account of the signal magnification of encoded SERS nanotags in addition to the high surface area to volume ratio of the nitrocellulose (NC) membrane, rapid quantification of the 11 pathogens with a broad linear dynamic range (LDR) and ultra-high sensitivity was achieved on one lateral flow microarray. Results: The limit of detection (LOD) for influenza A, parainfluenza 1, parainfluenza 3, respiratory syncytial virus, coxiella burnetii, legionella pneumophila, influenza B, parainfluenza 2, adenovirus, chlamydophila pneumoniae, and mycoplasma pneumoniae were calculated to be 0.031 pM, 0.030 pM, 0.038 pM, 0.038 pM, 0.040 pM, 0.039 pM, 0.035 pM, 0.032 pM, 0.040 pM, 0.039 pM, and 0.041 pM, respectively. The LDR of measurement of the target nucleic acids of the eleven RTI pathogens were 1 pM-50 nM, which span 5 orders of magnitude. Conclusions: We anticipate this novel approach could be widely adopted in the early and precise diagnosis of RTI and other diseases.
Assuntos
Nanopartículas Metálicas/química , Análise em Microsséries/métodos , Técnicas de Diagnóstico Molecular/métodos , Infecções Respiratórias/microbiologia , Análise Espectral Raman/métodos , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/patogenicidade , Colódio/química , Coxiella burnetii/genética , Coxiella burnetii/patogenicidade , Ouro/química , Humanos , Legionella pneumophila/genética , Legionella pneumophila/patogenicidade , Limite de Detecção , Análise em Microsséries/normas , Técnicas de Diagnóstico Molecular/normas , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/patogenicidade , Oligonucleotídeos/química , Orthomyxoviridae/genética , Orthomyxoviridae/patogenicidade , Testes Imediatos/normas , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/virologia , Análise Espectral Raman/normasAssuntos
Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Chlamydia/tratamento farmacológico , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Animais , Infecções por Chlamydia/microbiologia , Chlamydophila pneumoniae/efeitos dos fármacos , Chlamydophila pneumoniae/patogenicidade , Humanos , Testes de Sensibilidade MicrobianaRESUMO
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/metabolismoRESUMO
BACKGROUND: This study aims to investigate the chlamydia pneumoniae infection (PC) in patients with coronary heart disease. METHODS: A total of 92 patients with coronary heart disease, who were treated with percutaneous coronary intervention (PCI), were selected as the case group. In addition, 50 healthy people were enrolled as the control group. The incidences of CP infection and serum Chlamydia pneumoniae IgA antibody (CP-IgA), high sensitive C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were compared in these two groups. The classification of coronary artery lesion, the incidence of perioperative cardiovascular events, and adverse prognosis events within six months after procedure were compared. RESULTS: The incidence of CP infection in the case group was higher (42.4% vs. 0%, P < 0.05). Furthermore, 17 patients were at grade I, 39 patients were at grade II, and 36 patients were at grade III. The incidences for these three kinds of patients were 17.6, 30.8, and 66.7%. The incidence of CP infection at grade III was higher than that of grade I or II (P < 0.05). Serum CP-IgA, hs-CRP and IL-6 levels increased with the severity of the coronary artery disease (P < 0.05), and the serum hs-CRP and IL-6 levels of patients with perioperative cardiovascular events were higher (P < 0.05). Moreover, the serum CP-IgA levels of the patients with adverse prognosis events were also higher (P < 0.05). CONCLUSIONS: Patients with coronary heart disease have a high CP infection rate. The degree of infection is relevant to the severity of the coronary artery lesions and postoperative prognosis of patients, suggesting that CP infection may be an important factor affecting the incidence and prognosis of coronary heart disease.
Assuntos
Infecções por Chlamydophila/epidemiologia , Chlamydophila pneumoniae/patogenicidade , Doença das Coronárias/epidemiologia , Anticorpos Antibacterianos/sangue , Pequim/epidemiologia , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Infecções por Chlamydophila/sangue , Infecções por Chlamydophila/diagnóstico , Chlamydophila pneumoniae/imunologia , Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico , Doença das Coronárias/terapia , Feminino , Humanos , Imunoglobulina A/sangue , Incidência , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
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/microbiologiaRESUMO
INTRODUCTION: Chlamydia pneumoniae (Cp) is a bacterium that causes pneumonia and other respiratory diseases. Fever may be present early but absent by time of presentation to clinic. Increases in X-ray-confirmed pneumonia (XCP) and laboratory-confirmed Cp infections were observed in new soldiers in training at Fort Leonard Wood (FLW), Missouri, early in 2014. These findings prompted a site assistance visit from the U.S. Army Public Health Command, Aberdeen Proving Ground, Maryland, with a review of available data and information to describe the outbreak, and inspections of barracks and training facilities and review of training practices to identify opportunities for interventions to reduce the risk of respiratory disease agent transmission. MATERIALS AND METHODS: The study population was trainee soldiers at FLW in 2013-2014. Data from two acute respiratory disease surveillance systems were studied. A local surveillance system operated by the FLW General Leonard Wood Army Community Hospital Preventive Medicine Department tracked weekly chest X-rays taken and the numbers positive for pneumonia. A Naval Health Research Center, San Diego, California, laboratory-based Febrile Respiratory Illness Surveillance Program collected clinical data and nasal, or nasal and pharyngeal swabs, for nucleic acid amplification testing from up to 15 trainees/week with fever and either cough or sore throat. Up to 4 of the 15 specimens could be from afebrile patients with XCP. Specimens were tested for a variety of agents. RESULTS: Monthly rates of XCP rose quickly in 2014 and peaked at 0.9/100 trainees in May. The percentage of the San Diego surveillance system specimens that were positive for Cp also increased quickly in 2014, peaking at 54% in May. During the first half of 2014, the San Diego program studied specimens from 141 ill trainees; 37% (52/141) were positive for Cp, making it the most common organism identified, followed by rhinoviruses (8%), influenza viruses (4%), Mycoplasma pneumoniae (2%), and adenoviruses (1%). The remaining specimens (48%) were negative for all respiratory pathogens. Only 12% (6/52) of Cp positive patients were febrile. Facilities inspections and review of training practices failed to identify variables that might be contributing to an increased risk of respiratory agent transmission. CONCLUSION: The XCP rate and the percentage of specimens positive for Cp increased in early 2014, peaking in May. Only 12% of trainees with laboratory-confirmed Cp were febrile. Historically, acute respiratory disease surveillance at military training centers focused on febrile diseases, particularly those caused by adenoviruses. With introduction of an adenovirus vaccine in late 2011, respiratory disease rates dropped with only sporadic occurrences of adenovirus-associated disease. In 2012, the San Diego surveillance program began providing data on multiple respiratory disease agents, in addition to adenoviruses and influenza viruses. Since then, Cp, rhinoviruses and Mycoplasma pneumoniae have frequently been detected in trainees with acute respiratory disease. Respiratory surveillance programs supporting Army training centers should be re-evaluated in this post-adenovirus vaccine era, to include assessment of the fever criterion for selecting patients for study, the value of chest X-ray surveillance and the value of rapidly providing laboratory results to inform provider decisions regarding antibiotic use.