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At least 19 recordsLinked to original sources
PubMed2006

Therapeutic Chlamydophila abortus and C. pecorum vaccination transiently reduces bovine mastitis associated with Chlamydophila infection.

Infections with Chlamydophila abortus and C. pecorum are highly prevalent in cattle and have been associated with bovine mastitis. A prospective cohort study was conducted with a herd of 140 Holstein dairy cows to investigate the influence of Chlamydophila infection on subclinical inflammation of the bovine mammary gland as characterized by somatic cell numbers in milk. PCR detection of C. abortus and low serum antibody levels against Chlamydophila spp. were significantly associated with subclinical mastitis. To examine the effect of the infection by response modification, immune perturbation was done by two subcutaneous administrations of an experimental vaccine preparation of inactivated C. abortus and C. pecorum elementary bodies. Vaccination against Chlamydophila highly significantly decreased milk somatic cell numbers, thus reducing bovine mastitis, and increased antibody levels against Chlamydophila but did not eliminate shedding of C. abortus in milk as detected by PCR. The protective effect peaked at 11 weeks after vaccination and lasted for a total of 14 weeks. Vaccination with the Chlamydophila vaccine, a mock vaccine, or a combination vaccine against bovine viral diseases highly significantly increased C. abortus shedding in milk for 1 week, presumably mediated by the vaccine adjuvant. In summary, this study shows an etiological involvement of the widespread Chlamydophila infections in bovine mastitis, a herd disease of critical importance for the dairy industry. Furthermore, this investigation shows the potential for temporary improvement of chlamydial disease by therapeutic vaccination. Chlamydophila vaccination of cattle might serve as a testing ground for vaccines against human chlamydial infections.

Animals↗
PubMed2006

Associations between Chlamydophila infections, schizophrenia and risk of HLA-A10.

Several microbes have been suspected as pathogenetic factors in schizophrenia. We have previously observed increased frequencies of chlamydial infections and of human lymphocyte antigen (HLA)-A10 in independent studies of schizophrenia. Our aim here was to analyze frequencies of three types of Chlamydiaceae in schizophrenic patients (n=72), random controls (n=225) and hospital-patient controls (n=36), together with HLA-A genotypes. Patients were diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders-IV. Blood samples were collected at the beginning of hospitalization and analyzed with Chlamydiaceae species-specific polymerase chain reaction (PCR). Control panels consisted of randomly selected volunteers and hospitalized, non-schizophrenic patients. We found chlamydial infection in 40.3% of the schizophrenic patients compared to 6.7% in the controls. The association of schizophrenia with Chlamydiaceae infections was highly significant (P=1.39 x 10(-10), odds ratio (OR)=9.43), especially with Chlamydophila psittaci (P=2.81 x 10(-7), OR=24.39). Schizophrenic carriers of the HLA-A10 genotype were clearly most often infected with Chlamydophila, especially C. psittaci (P=8.03 x 10(-5), OR=50.00). Chlamydophila infections represent the highest risk factor yet found to be associated with schizophrenia. This risk is even further enhanced in carriers of the HLA-A10 genotype.

Adult↗
PubMed2006

Effect of PEX, a noncatalytic metalloproteinase fragment with integrin-binding activity, on experimental Chlamydophila pneumoniae infection.

Chlamydophila pneumoniae is a pathogen that is involved in acute and chronic respiratory infections and that is associated with asthma and coronary artery diseases. In this study, we evaluated the effects of PEX, a noncatalytic metalloproteinase fragment with integrin-binding activity, against experimental infections caused by C. pneumoniae. Moreover, we investigated the relationships between C. pneumoniae and alpha(v)beta(3) integrin functions in order to explain the possible mechanism of action of PEX both in vitro and in vivo. For the in vitro experiments, HeLa cells were infected with C. pneumoniae and treated with either PEX or azithromycin. The results obtained with PEX were not significantly different (P > 0.05) from those achieved with azithromycin. Similar results were also obtained in a lung infection model. Male C57BL/J6 mice inoculated intranasally with 10(6) inclusion-forming units of C. pneumoniae were treated with either PEX or azithromycin plus rifampin. Infected mice treated with PEX showed a marked decrease in C. pneumoniae counts versus those for the controls; this finding did not differ significantly (P > 0.05) from the results observed for the antibiotic-treated group. Integrin alpha(v)beta(3) plays an important role in C. pneumoniae infection. Blockage of integrin activation led to a significant inhibition of C. pneumoniae infection in HeLa cells. Moreover, CHO(DHFR) alpha(v)beta(3)-expressing cells were significantly (P < 0.001) more susceptible to C. pneumoniae infection than CHO(DHFR) cells. These results offer new perspectives on the treatment of C. pneumoniae infection and indicate that alpha(v)beta(3) could be a promising target for new agents developed for activity against this pathogen.

Animals↗
PubMed2003

Application of touchdown enzyme time release (TETR)-PCR for diagnosis of Chlamydophila abortus infection.

Chlamydophila abortus-DNA was detected using a touchdown enzyme time-release (TETR)-polymerase chain reaction (PCR) assay as an improved test for sensitive and rapid diagnosis of abortion in small ruminants. Two hundred and fifty two placentae, liver or spleen tissue samples from aborting ewes and goats or aborted lambs and kids in which C. abortus infection was suspected were examined by TETR-PCR and the results were compared with cell culture. Sixty-five tissue samples were found to be TETR-PCR positive while only 56 samples were cell culture-positive. After resolution of discrepant samples with a confirmatory nested PCR assay, TETR-PCR had a sensitivity of 97% and a specificity of 99.5% while culture had a sensitivity of 84.8% and a specificity of 100%. The analytical sensitivity of the TETR-PCR assay was determined with DNA extracted from 4-fold serial dilution of C. abortus B577 culture and found to be 0.25 inclusion-forming unit per PCR. No reduction in the analytical sensitivity was noted when the assay was tested with mouse liver samples spiked with 4-fold serial dilution of C. abortus B577 culture. No target product was amplified when DNA from Chlamydophila pecorum was tested. TETR-PCR used in this study is a practical, rapid, sensitive and specific assay that could be used for the detection of C. abortus in infected tissue samples. We recommend the use of this assay as a supplemental diagnostic tool for detection of C. abortus in infected tissue samples.

Abortion, Veterinary↗
PubMed2006

Tissue MicroArray (TMA) analysis of normal and persistent Chlamydophila pneumoniae infection.

BACKGROUND: Chlamydophila pneumoniae infection has been implicated as a potential risk factor for atherosclerosis, however the mechanism leading to persistent infection and its role in the disease process remains to be elucidated. METHODS: We validated the use of tissue microarray (TMA) technology, in combination with immunohistochemistry (IHC), to test antibodies (GroEL, GroES, GspD, Ndk and Pyk) raised against differentially expressed proteins under an interferon-gamma (IFN-gamma) induced model of chlamydial persistence. RESULTS: In the cell pellet array, we were able to identify differences in protein expression patterns between untreated and IFN-gamma treated samples. Typical, large chlamydial inclusions could be observed in the untreated samples with all antibodies, whereas the number of inclusions were decreased and were smaller and atypical in shape in the IFN-gamma treated samples. The staining results obtained with the TMA method were generally similar to the changes observed between normal and IFN-gamma persistence using proteomic analysis. Subsequently, it was shown in a second TMA including archival atheromatous heart tissues from 12 patients undergoing heart transplantation, that GroEL, GroES, GspD and Pyk were expressed in atheromatous heart tissue specimens as well, and were detectable morphologically within lesions by IHC. CONCLUSION: TMA technology proved useful in documenting functional proteomics data with the morphologic distribution of GroEL, GroES, GspD, Ndk and Pyk within formalin-fixed, paraffin-embedded cell pellets and tissues from patients with severe coronary atherosclerosis. The antibodies GroEL and GroES, which were upregulated under persistence in proteomic analysis, displayed positive reaction in atheromatous heart tissue from 10 out of 12 patients. These may be useful markers for the detection of persistent infection in vitro and in vivo.

Cell Line↗
PubMed2006

NF-kappaB and inhibitor of apoptosis proteins are required for apoptosis resistance of epithelial cells persistently infected with Chlamydophila pneumoniae.

Infection with Chlamydophila pneumoniae (Cpn) renders host cells resistant to apoptosis induced by a variety of stimuli. While modulation of apoptosis has been extensively studied in cells acutely infected with Cpn, very little is known on how persistent chlamydial infection influences host cell survival. Here we show that epithelial cells persistently infected with Cpn resist apoptosis induced with TNFalpha or staurosporine. Cpn induced the activation of nuclear factor kappa B (NF-kappaB) and inhibition of NF-kappaB with a chemical inhibitor or by silencing expression of the p65 subunit sensitized infected cells for apoptosis induction by staurosporine or TNFalpha. Persistent infection resulted in the upregulation of the NF-kappaB regulated inhibitor of apoptosis protein 2 (cIAP-2) but not inhibitor of apoptosis protein 1 (cIAP-1). Interestingly, silencing of either cIAP-1 or cIAP-2 sensitized infected cells, suggesting that IAPs play an important role in the apoptosis resistance of persistently infected cells.

Apoptosis↗
PubMed2005

Influence of the Th2 immune response established by Nippostrongylus brasiliensis infection on the protection offered by different vaccines against Chlamydophila abortus infection.

Chlamydophila abortus is the aetiological agent of enzootic abortion in small ruminants in which it infects the placenta to cause abortion during the last trimester of gestation. In a mouse model, a Th1 immune response involving IFN-gamma production and CD8+ T cells is necessary for the infection to be resolved. The authors previously demonstrated that infection with Nippostrongylus brasiliensis, a rodent gastrointestinal nematode extensively used in experimental models to induce Th2 responses, alters the specific immune response against C. abortus infection, increasing bacterial multiplication in liver and reducing specific IFN-gamma production. The aim of the present work was to clarify whether a Th2 immune response has any influence on the success of vaccination using both inactivated and attenuated vaccines. The results showed that the Th2 response established prior to vaccination did not influence the induction of protection offered by the vaccines. However, the effectiveness of this protective response can be altered, depending on the adjuvant employed in the inactivated vaccines, when the Th2 response is established after vaccination, just before challenge with C. abortus.

Animals↗
PubMed2004

[Relationship between the peripheral arterial occlusive disease and the infection by Chlamydophila pneumoniae].

BACKGROUND AND OBJECTIVE: The relationship between peripheral arterial occlusive disease (PAOD) and Chlamydophila pneumoniae infection was studied by analyzing clinical samples from 95 patients with PAOD (cases) and 100 controls. PATIENTS AND METHOD: The following investigations were conducted: IgG and IgA against lipopolysaccharide (LPS) and against purified C. pneumoniae-specific antigens from elementary bodies (EB) with ELISA; anti-EB IgG, with MIF; C. pneumoniae DNA in arterial biopsy and peripheral blood leukocyte cells (PBLCs) with heminested PCR; LPS with ELISA; and bacteria culture in HEp-2 cells from arterial biopsy. RESULTS: The percentage of positive results in cases and controls groups for anti-LPS IgG was: 21% and 14%, respectively, with no differences; nor were there any differences with IgA (22 and 21%, respectively). However, differences were seen in the anti-EB IgG between cases (74% and 72%, for ELISA and MIF, respectively) and controls (31% and 34%). There were no differences in anti-EB IgA. Bacterial DNA was detected in 67% of atheromatous plaques (cases) vs. 12% of pudendal arteries (controls) (p = 0.0001). No C. pneumoniae DNA and LPS was detected in PBLCs and biopsic samples, respectively; and no C. pneumoniae strain could be recovered by cell culture from cases. CONCLUSIONS: On the basis of our results, PAOD is significantly associated with C. pneumoniae infection through the detection of anti-EB IgG from serum and bacterial DNA from arterial biopsy.

Aged↗
PubMed2006

Involvement of TNFalpha -308A promoter polymorphism in the development of asthma in children infected with Chlamydophila pneumoniae.

Several data indicate a connection between Chlamydophila pneumoniae infection and asthma. Although C. pneumoniae is a common cause of infection, not all infected patients develop asthma. This suggests that certain individuals may be genetically predisposed to the chronic effects of C. pneumoniae infection on airway functions. We investigated the possible modifying effect of different polymorphisms on C. pneumoniae infection and on the susceptibility to asthma in 318 children, among those 144 had asthma and 174 had no asthmatic symptoms. C. pneumoniae-specific antibodies were measured by ELISA. Tumor necrosis factor-alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), and RANTES (regulated on activation normal T cell expressed and secreted) genotypes were determined by PCR-restriction fragment length polymorphism (RFLP). There were no significant differences in the percentage of children positive for C. pneumoniae-specific antibodies between cases and controls. None of the genotypes was associated with altered susceptibility to C. pneumoniae infection. Among asthmatic children carrying the TNFalpha -308A allele, there were significantly more patients positive for C. pneumoniae-specific IgG, than among control children carrying the same allele (20.1% versus 9.2% of asthmatic versus control children, respectively; p = 0.002; odds ratio = 3.52 (1.52-7.53); p = 0.005). This study indicates the possible roles of polymorphisms in the immune system in the susceptibility to asthma in children infected with C. pneumoniae.

Adolescent↗
PubMed2005

Use of quantitative real-time PCR to monitor the response of Chlamydophila felis infection to doxycycline treatment.

Fifteen cats infected with Chlamydophila felis were monitored for the presence of C. felis DNA on ocular swabs by using real-time PCR and for clinical signs of disease. The cats were assigned to three groups: oral doxycycline at 10 mg/kg of body weight/day for 7 days (six cats), oral doxycycline at 10 mg/kg/day for 14 days (five cats), and an untreated control group (four cats). The untreated cats remained positive for C. felis throughout the trial; clinical signs were most severe on days 14 to 21 postinfection, and then they declined. Treatment with 7 and 14 days of doxycycline decreased C. felis relative copy numbers and clinical signs rapidly. C. felis became undetectable in some of the cats during or after treatment. However, after the cessation of treatment, a recurrence of high relative copy numbers of C. felis and severe clinical signs in all cats was seen. Rescue treatment with 21 days of doxycycline was successful at eliminating infection in eight of the cats; a further 28 days of doxycycline was required to eliminate infection in the remaining three cats. It was concluded that 7, 14, and, in some cases, 21 days of treatment with oral doxycycline will not eliminate C. felis infection. At least 28 days of treatment with doxycycline is required to ensure elimination of the organism. Real-time PCR is a sensitive technique for monitoring C. felis infection and the response to antibiotic treatment.

Animals↗
PubMed2004

Natural killer (NK) cells play a critical role in the early innate immune response to Chlamydophila abortus infection in mice.

Chlamydophila abortus, the aetiological agent of ovine enzootic abortion, induces a strong inflammatory reaction that leads to the T helper cell (Th1) specific immune response necessary for the clearance of infection. Because the role of natural killer (NK) cells during the first stages of this response has received little attention, this study focused on determining the function of these cells in a mouse model of infection. The location of NK cells in the liver and spleen of infected mice was examined immunohistochemically with an anti-Ly49G monoclonal antibody. The number of NK cells increased during the infection both in spleen and liver. In subsequent experiments, an anti-asialo GM1 polyclonal antibody was injected to deplete the NK cells. NK-depleted mice showed a substantial increase in their susceptibility to C. abortus infection, with high mortality rates and an increased burden of bacteria in the liver. Histopathological studies showed that inflammatory foci, composed mainly of neutrophils, were greater in size and number in depleted mice, while numerous chlamydial inclusions were associated with the foci. Serum concentrations of IFN-gamma, a key cytokine in the control of C. abortus infection, were substantially reduced in the NK-depleted mice. To establish the relationship between NK cells and other components of the innate immune response, neutrophils were depleted with the RB6-8C5 antibody. These cells were shown to be crucial in the recruitment of NK cells to the inflammatory foci.

Animals↗
PubMed2006

Validation of an internal method for the diagnosis of infections with Chlamydophila abortus and Coxiella burnetii by real-time multiplex PCR.

Chlamydophila abortus and Coxiella burnetii are one of the major pathogens implicated in abortion in cattle. Their characteristic of obligate intracellular bacteria, and of zoonotic agents, makes their culture difficult in diagnostic laboratories, and the traditional tools of diagnosis (detection of sera antibodies by ELISA, Stamp's coloration) encounter specificity, sensitivity and interpretability limits. Individual PCR have recently been developed. Nevertheless, their income/cost is a limiting factor for breeders. As the symptoms are not specific, the request for analysis often concerns the two valences. Consequently, the development and the validation of an internal multiplex PCR appears to be a suitable solution.

Abortion, Veterinary↗
PubMed2002

B-cell-deficient mice show an exacerbated inflammatory response in a model of Chlamydophila abortus infection.

The resolution of Chlamydophila abortus (Chlamydia psittaci serotype 1) infection is dependent on gamma interferon and CD8(+) T cells, and classically, B cells have been considered to play a minimal role in host defense. The role of B cells in the immune response was studied by using a model of infection in mice with genetically modified immunoglobulin M transmembrane domains ( micro MT). In the absence of B cells, infection with C. abortus leads to an acute severe fatal disease that involves a disseminated intravascular coagulation syndrome. micro MT mice displayed an increased level of proinflammatory cytokines in serum, and an increased number of neutrophils was observed in the lesions. The possible deleterious role of neutrophils in the pathogenesis of disease in micro MT mice was determined by depletion of the neutrophils with the monoclonal antibody RB6-8C5. This led to an enhancement of the bacterial burden and early mortality in both micro MT and wild-type mice, while necrotic lesions remained. Analysis of the presence of immunoregulatory cytokines showed significantly lower levels of transforming growth factor beta in the sera of micro MT mice. However, mice lacking mature B cells were able to establish a specific immune response that protected them from a secondary challenge. Taken together, these data suggest an immunomodulatory role for B cells in the early events of C. abortus primary infection that can protect mice against an exaggerated inflammatory response.

Animals↗
PubMed2004

High prevalence of natural Chlamydophila species infection in calves.

We investigated the acquisition and prevalence of Chlamydophila sp. infection in calves. Specimens were collected at weekly intervals from birth to week 12 postpartum from 40 female Holstein calf-dam pairs in a dairy herd. Real-time PCR detected, quantified, and differentiated Chlamydophila 23S rRNA gene DNA from vaginal cytobrush swabs and milk samples. Chemiluminescence enzyme-linked immunosorbent assay with lysed Chlamydophila abortus or Chlamydophila pecorum elementary body antigens quantified antibodies against Chlamydophila spp. in sera. Chlamydophila sp. DNA was found in 61% of calves and 20% of dams in at least one positive quantitative PCR. In calves, clinically inapparent C. pecorum infection with low organism loads was fivefold more prevalent than C. abortus infection and was most frequently detected by vaginal swabs compared to rectal or nasal swabs. In dams, C. abortus dominated in milk and C. pecorum dominated in the vagina. The group size of calves correlated positively (P < 0.01) with Chlamydophila infection in quadratic, but not linear, regression. Thus, a doubling of the group size was associated with a fourfold increase in frequency and intensity of Chlamydophila infection. For groups of 14 or 28 calves, respectively, logistic regression predicted a 9 or 52% probability of infection of an individual calf and a 52 or 99.99% probability of infection of the group. Anti-Chlamydophila immunoglobulin M antibodies in Chlamydophila PCR-positive calves and dams and in dams that gave birth to calves that later became positive were significantly higher than in PCR-negative animals (P </= 0.02). Collectively, crowding strongly enhances the frequency and intensity of highly prevalent Chlamydophila infections in cattle.

Animals↗
PubMed2006

Comparison of fetal and maternal inflammatory responses in the ovine placenta after experimental infection with Chlamydophila abortus.

Placentae from 13 pregnant ewes infected intravenously with Chlamydophila abortus, together with placentae from nine uninfected control ewes, were examined at 14, 21 or 28 days post-inoculation (p.i.). Chlamydial inclusions were present in the trophoblast at 14 days p.i. and were widespread by 21 days p.i. Chorioallantoic lesions (oedema, arteritis and thrombosis) were severe at 28 days p.i., the changes being particularly marked in the membrane surrounding placentomes. Lymphocytes constituted only a small proportion of the cellular infiltrate in the chorioallantois; neutrophil infiltration of the chorionic surface was evident where the trophoblast layer had sloughed, whereas macrophages represented the predominant cell type in the deeper stroma. In contrast, on the maternal side of the placenta, chlamydial inclusions were sparse at all timepoints, and even at 28 days p.i., lesions were restricted to focal endometritis at the placentomal limbus and occasional foci of septal necrosis. T lymphocytes were numerous within endometrial and septal lesions, the infiltrate consistently containing more CD8(+) than CD4(+) cells. The fetal response to chlamydial invasion of the placenta was innate in character, whereas the maternal response appeared to represent an acquired, chlamydia-specific immune response.

Animals↗
PubMed2005

Immunopathology of Chlamydophila abortus infection in sheep and mice.

Chlamydophila abortus targets the placenta, causing tissue damage, inflammation and abortion (enzootic abortion of ewes). It is one of the main infectious causes of abortion in ewes, resulting in major economic losses to agricultural industries worldwide. Although ruminants and pigs are the principal hosts, humans are also susceptible to infection. Control of disease requires a host inflammatory response, which is likely to contribute to pathology and abortion. Mouse models have been widely used to provide insight into the role of specific immune cells in controlling infection and disease. The use of such model systems for investigating the mechanisms of abortion, latency, persistence, and immunity to reinfection will result in the identification of novel vaccine control strategies for sheep.

Abortion, Veterinary↗
PubMed2003

Chronic Chlamydophila pneumoniae infection in lung cancer, a risk factor: a case-control study.

The relationship between chronic Chlamydophila (formerly Chlamydia) pneumoniae infection and lung carcinoma was investigated. A total of 123 patients who were smokers and diagnosed with lung carcinoma based on clinical and laboratory (radiological, cytological) findings were examined. Of these patients, 70 had small-cell, 28 squamous-cell and seven large-cell carcinomas, while 18 had adenocarcinoma. A total of 123 healthy persons matching patients in age, sex, duration of smoking and locality were chosen as controls. Blood samples (5 ml) were withdrawn at the time of diagnosis and 1 month later. The values between IgG >/= 512 and IgA >/= 40 were set as the criteria for chronic Chlamydophila pneumoniae infections. In male patients with lung carcinoma, Chlamydophila pneumoniae IgG antibody titres of >/= 512 and IgA antibody titres of >/= 40 were found at a higher rate than in the control group. This ratio was not significant for the female patients. In chronic Chlamydophila pneumoniae infections, Chlamydophila pneumoniae antibody titres with values IgG >/= 512 and IgA >/= 40 were found in a total of 62 (50.4 %) cases. Chronic Chlamydophila pneumoniae infections were seen statistically more often in male patients with carcinoma who were aged 55 years or younger. This study supports the idea that chronic Chlamydophila pneumoniae infection increases the risk of lung carcinoma.

Adult↗
PubMed2001

[Analysis of occurrence of Chlamydophila pneumoniae infection serological markers in patients with bronchial asthma].

Numerous publications pointing the role of Chlamydophila pneumoniae infections in etiopathogenesis of bronchial asthma have appeared in recent years. Up to the presence the diagnostics of Chlamydophila pneumoniae infections has been based on the serological examinations especially on indirect microimmunofluorescence which is regarded to be a "gold standard". The aim of the paper was to compare the occurrence of Chlamydophila pneumoniae infection serological markers in the group of patients with asthma (N = 38) and in the control group (N = 38). The obtained results have allowed making the following conclusions: 1. The increased level of IgG class anti-Chlamydophila pneumoniae antibodies in the group of patients with asthma, which proves more frequent contact with Chlamydophila pneumoniae in that group, seems to support the hypothesis about the role of chlamydial infections in etiopathogenesis of bronchial asthma. 2. The single assessment of anti-Chlamydophila pneumoniae antibodies in the ELISA test has not allowed determining the type of chlamydial infection in unambiguous way. However, with reference to the entire clinical picture, the statement of the contact with Chlamydophila pneumoniae can be helpful especially in the treatment of severe asthma.

Asthma↗