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Estrogens and Chlamydia trachomatis.

Isolates of Chlamydia trachomatis were inoculated in nonreplicating McCoy cells and incubated for 48 hr with various concentrations of hormones. Only the estrogens, particularly 17-beta-estradiol, had an affect on the subsequent infection of the McCoy cells by the Chlamydia. Exposure to 2-4 ng/ml (10(-8) M) estradiol during inoculation and incubation was associated with no change in the initial binding of Chlamydia to McCoy cells, but significantly more (about twofold) Chlamydia inclusions in the McCoy cells after 48 hr incubation. This effect was dose dependent, could be blocked with anti-estrogens, and also occurred with replicating McCoy cells. Localization studies suggest that this effect on the infectivity of Chlamydia trachomatis is dependent upon initial interactions of estrogens with McCoy cells. Both light microscopy and electron microscopy of the McCoy (fibroblast) cells showed no morphological changes after exposure to the estrogens under the incubation conditions employed in these studies. Estrogens may modify host susceptibility to Chlamydia infections in a manner independent of morphological changes in mammalian cells.

Animals↗

Functional characterization of class Ia- and non-class Ia-restricted Chlamydia-reactive CD8+ T cell responses in humans.

CD8(+) T cells are a key immune component for the eradication of many intracellular pathogens. This study aims to characterize the human CD8(+) T cell response to naturally processed chlamydial Ags in individuals exposed to the intracellular pathogen Chlamydia trachomatis. By using C. trachomatis-infected autologous dendritic cells (DCs) as stimulators, Chlamydia-reactive CD8(+) T cell responses were detected in all 10 individuals tested. The majority of the Chlamydia-reactive CD8(+) T cells were non-MHC class Ia restricted in all three of the individuals tested. From one donor, three non-class Ia-restricted and two class Ia-restricted Chlamydia-specific CD8(+) T cells were cloned and characterized further. All five T cell clones secreted IFN-gamma in response to autologous DCs infected with viable Chlamydia, but not with DCs pulsed with inactivated chlamydial elementary bodies. MHC class Ia-restricted and non-class Ia-restricted responses were inhibited by DC treatment with a proteasomal inhibitor and an endoplasmic reticulum-Golgi transport inhibitor, suggesting that these T cells recognize a peptide Ag translocated to the host cell cytosol during infection that is processed via the classical class Ia Ag-processing pathway. Even though both restricted and nonrestricted CD8(+) T cells produced IFN-gamma in response to Chlamydia-infected fibroblasts, only the non-class Ia-restricted cells were lytic for these targets. The class Ia-restricted CTLs, however, were capable of cytolysis as measured by redirected killing. Collectively, these data demonstrate that both class Ia-restricted and non-classically restricted CD8(+) T cells are elicited in C. trachomatis-exposed individuals. Their role in host immunity remains to be elucidated.

Antigen Presentation↗

Human CD8+ T cells recognize the 60-kDa cysteine-rich outer membrane protein from Chlamydia trachomatis.

The intracellular bacterial pathogen Chlamydia is sequestered from the host cell cytoplasm by remaining within an inclusion body during its replication cycle. Nevertheless, CD8(+) T cells recognizing Chlamydia Ags in the context of MHC class I molecules are primed during infection. We have recently described derivation of Chlamydia-specific human CD8(+) T cells by using infected dendritic cells as a surrogate system to reflect Chlamydia-specific CD8(+) T cell responses in vivo. These CD8(+) T cell clones recognize chlamydial Ags processed via the conventional class Ia processing pathway, as assessed by treatment of infected APC with lactacystin and brefeldin A, suggesting that the Ags are translocated from the chlamydial inclusion into the host cell cytosol. In this study, outer membrane protein 2 (OmcB) was identified as the Ag recognized by one of these Chlamydia-specific human CD8(+) T cells, and we defined the HLA*A0101-restricted epitope from this Ag. CD8(+) T cell responses to this epitope were present at high frequencies in the peripheral blood of both of two HLA*A0101 donors tested. In vitro chlamydial growth was completely inhibited by the OmcB-specific CD8(+) T cell clone independently of lytic mechanisms. OmcB is a 60-kDa protein that has been postulated to be associated with the Chlamydia outer membrane complex. The subcellular localization of OmcB to the cytosol of infected cells, as determined by conventional MHC class I Ag processing and presentation, suggests the possibility of an additional, cytosolic-associated function for this protein.

Adolescent↗

[Chlamydia pneumoniae and atherosclerosis].

There is widespread consensus that atherosclerosis is an inflammatory disease. Between possible pathogenetic mechanisms, infective hypothesis has received increasing attention. Researches have recently focused their attention on the role of Chlamydia pneumoniae, a gram-negative intracellular organism, as infection by this bacterium has been demonstrated frequently associated with atherosclerosis. This review attempts to analyze and critically evaluate available data of the literature about the association between Chlamydia pneumoniae and atherosclerosis in order to provide updated elements of judgement concerning a possible future revolutionary scenario: the consideration of atherosclerosis as an infective disease, susceptible to prevention and treatment by means of antimicrobial therapy. More than twenty sero-epidemiological studies have found a two-fold or greater risk of cardiovascular events in subjects with serological evidence of Chlamydia pneumoniae infection. The organism has been identified in over 50% of atherosclerotic plaques examined by various histopathological techniques, while it has been only rarely found in normal artery tissues; moreover, viable Chlamydia pneumoniae has recently been isolated from coronary and carotid atherosclerotic plaques. Several experimental studies have shown that the biological properties of Chlamydia pneumoniae can explain its potential role in initiating and/or modulating plaque formation. The most relevant issue, i.e. the possibility of preventing or slowing progression of the disease with antimicrobial treatment, is still unsolved: only data from experimental studies on animals and four small intervention trials on humans are available, and their encouraging results require confirmation in larger prospective studies. In conclusion, while the association between Chlamydia pneumoniae and atherosclerosis seems to be established, it is still uncertain whether or not the organism plays a causal role in atherosclerosis and its complications. It is hoped that the results of wide scale clinical intervention trials with antibiotics for the secondary prevention of atherosclerotic diseases now in progress will clarify this problem.

Arteriosclerosis↗

[Coxiella burnetii infections and infections with bacteria of the genus Chlamydia in dairy cattle].

Comparative studies on the prevalence of infections caused by Coxiella burnetii (C. burnetii) and Chlamydia were carried out with 592 cattle older than 2 years and 234 cattle younger than 2 years. Of these 477 originated from 24 dairy herds with considerable fertility problems (positive herds) and 349 from 14 dairy herds without major fertility problems (control herds). For the direct detection of these pathogens in the genitals capture ELISAs were employed, for the demonstration of antibodies the complement fixation test (CFT). Direct detection of C. burnetii and Chlamydia single as well as mixed infection revealed significant higher values for cattle from positive herds compared with those from the control herds. Animals revealing insemination ratios of > or = 2 showed significantly more frequent excretion of Chlamydia via the genitals and antibodies against C. burnetii than cattle with an insemination ratio of < 2. Investigations of cows which had had an abortion showed no indications of significantly more frequent C. burnetii or chlamydial infections. Inseminated but non-pregnant cows excreted significantly more C. burnetii and Chlamydia than pregnant cows. Clinical signs of endometritis were associated with an enhanced excretion of Chlamydia. Animals younger than 2 years excreted significantly more frequently C. burnetii but not Chlamydia via the genitals than animals older than 2 years. Indirect test showed results vice versa.

Abortion, Veterinary↗

Acrosome reaction in Chlamydia-positive and negative patients.

Chlamydia trachomatis infections might have a detrimental effect on various sperm functions. Data concerning the effect of C. trachomatis on the capacitation activity of sperms are lacking. The study was undertaken to evaluate whether chlamydial infection influences acromsome reaction (AR). Three groups of men were investigated for ARs -Chlamydia negative (n = 46) and positive (n = 30) patients, and healthy men (n = 53) undergoing vasectomy. The fluorescence technique for the evaluation of AR was applied. The normal range for the induction of AR was assumed DeltaAR > 12.5% for this technique. Seminal plasma was examined for IgA antibodies against C. trachomatis. There was a significant difference in AR between healthy volunteers, Chlamydia-negative and Chlamydia-positive patients. DeltaARs were 15.8 +/- 1.6% in healthy volunteers versus 12.15 +/- 2.4% in Chlamydia-negative and 9.08 +/- 1.8% in Chlamydia-postive patients, respectively (P < 0.05). Significant elevated titres of C. trachomatis-specific IgA in seminal plasma showed a negative correlation with the AR of spermatozoa. AR seems to be a valuable marker, especially in couples with idiopathic infertility.

Acrosome Reaction↗

[Role of Chlamydia, mycoplasma and cytomegalovirus infection in the development of coronary artery disease].

AIM: To assess relationship between some infection factors and presence of coronary heart disease. MATERIAL: Patients with myocardial infarction (n=56), unstable angina (n=50), stable angina (n=50) and age - matched controls (n=49). METHODS: Levels of IgG, IgM, IgA antibodies to Chlamydia pneumonia, Chlamydia trachomatis, Chlamydia psittaci, IgG, IgM antibodies to Cytomegalovirus, and also of antibodies and antigen to Mycoplasma pneumoniae were measured in blood serum. RESULTS: Compared with controls patients with coronary heart disease had higher frequency of seropositivity to Chlamydia pneumonia, Mycoplasma pneumonia and Cytomegalovirus (p< 0.05 ) and similar levels of seropositivity to Chlamydia trachomatis and Chlamydia psittaci. Infectious burden (quantity of antibodies per one patient) was significantly higher in patients with myocardial infarction, unstable and stable angina than in controls (1.58, 1.42, 1.41 and 0.95, respectively). CONCLUSION: Our results confirm presence of association between infection and coronary heart disease.

Adult↗

[Studies on the infection status of seven species Mycoplasma, three species of Chlamydia, Neisseria gonorrhoeae and Garderella vaginalis in 76 patients with sexual transmitted diseases].

OBJECTIVE: To study the infectious status of seven species of Mycoplasma, three species of Chlamydia, Neisseria gonorrhoeae and Garderella vaginalis in the 76 male sexual transmitted disease (STD) patients in Yangzhou city. METHODS: Twelve species of pathogens including Ureaplasma urealyticum (Uu), Mycoplasma hominis (Mh), Mycoplasma pneumoniae (Mpn), Mycoplasma genitalium (Mg), Mycoplasma fermentans (Mf), Mycoplasma penetrans (Mpe), Mycoplasma prium (Mpi), Chlamydia trachomatis (Ct), Chlamydia pneumoniae (Cpn), Chlamydia psittaci (Cps), Neisseria gonorrhoeae (Ng) and Garderella vaginalis (GV) were detected by nested polymerase chain reaction including PPNG. RESULTS: The positive rates of Uu, Mh, Mpn, Mg, Mf, Mpe, Ct, Ng were 64.5%, 27.6%, 26.3%, 18.4%, 2.6%, 2.6%, 31.6%, 36.8%, in which Penicillinase-producing neisseria gonorrhoeae (PPNG) accounted for 14.3%, GV 15.8%. No Mpi, Cpn or Cps were found. There was more significant therapeutic effects on the detectable rate of Mycoplasma nucleic acid between positive gonococcus and negative gonococcus in male STDs patients (chi(2) = 3.848, P < 0.05). CONCLUSION: The infection rates of Mycoplasma, Chlamydia, Ng and GV were high among male STD patients in Yangzhou city. In clinical practice, more attention should be paid on correct diagnosis and treatment for patients, with Gonococcus, Chlamydia, Mycoplasma and GV.

Adult↗

Chlamydia shedding by four species of wild birds.

Four wild bird species--great-tailed grackle (Cassidix mexicanus), common grackle (Quiscalus quiscula), brown-headed cowbird (Molothrus ater), and mourning dove (Zenaidura macroura)--were either inoculated intratracheally with Chlamydia psittaci or exposed indirectly as uninoculated cagemates. Shedding of chlamydiae was monitored by inoculating mice with suspensions of material eluted from cloacal swabs collected from all birds, usually at 3-day intervals. Sporadic shedding of chlamydiae was demonstrated in three species (great-tailed grackle, brown-headed cowbird, and mourning dove) that were inoculated, and also in uninoculated grackles of both species exposed to inoculated great-tailed grackles. All inoculated birds except one mourning dove developed antibody detectable by complement-fixation (CF). Of the exposed birds, only grackles had antibody. However, two great-tailed grackles which did shed chlamydiae did not develop CF antibody. The modified direct CF (MDCF) method was slightly more sensitive than the direct CF method. The agar-gel precipitin method was not entirely reliable for antibody detection, for it did not correlate with CF serology and shedding of chlamydiae. It is concluded that: 1) grackles are potential reservoir hosts that could be important in the transmission cycle of C. psittaci in nature; and 2) epidemiologic studies of chlamydiosis in wild birds should include both serologic testing (preferably by the MDCF method) and attempts to isolate chlamydiae from cloacal swabs.

Animals↗

Chlamydia pneumoniae infection in acute exacerbations of COPD.

Chlamydia pneumoniae, strain TWAR, is a frequent causative agent of acute respiratory disease. We assessed the incidence and prevalence of Chlamydia pneumoniae infections in COPD. We studied, from January 1990 to May 1991, 142 out-patients with acute purulent exacerbations of chronic obstructive pulmonary disease (COPD) and 114 healthy control subjects. Oropharyngeal swab specimens were collected at each exacerbation and analysed using a high definition monoclonal indirect fluorescent antibody test for Chlamydia pneumoniae identification. Immunoglobulins G and M (IgG and IgM) fractions of antibodies to Chlamydia pneumoniae were studied by microimmunofluorescence test. Prevalence of specific IgG was 63% in COPD, and 46% in controls (Chi-squared test p = 0.007). Moreover, mean titre of IgG was significantly higher in COPD than in controls. Five patients were positive for specific IgM (> or = = 1:16), and one had a fourfold increase of IgG titre; four of these patients had been treated with ciprofloxacin 1 g.day-1 for 10 days, and two with erythromycin, 3 g.day-1 for 14 days, with remission of signs and symptoms of exacerbation. Chlamydia pneumoniae identification was always negative. Our data suggest that Chlamydia pneumoniae infection is a rather frequent event in COPD, since at least 4% of exacerbations may be associated with it.

Acute Disease↗

A national survey of nurse practitioner chlamydia knowledge and treatment practices of female patients.

Chlamydia is the most prevalent sexually transmitted disease in the United States, with over 4 million new infections presenting each year. The disease presents disproportionate problems for women who are generally asymptomatic; chlamydia is more difficult to diagnose in women than men. Untreated infections in women evolve into serious reproductive tract sequelae, including pelvic inflammatory disease, chronic pain, infertility, ectopic pregnancy, and neonatal complications. The bright side to this epidemic is that these sequelae are preventable. Chlamydia is both treatable and easily cured when it is detected. A national mailed survey of NPs was conducted to ascertain current chlamydia knowledge levels and clinical practices with female patients. Survey findings indicate that NPs are fairly knowledgeable about the infection and NP clinical practices are generally consistent with Centers for Disease Control and Prevention recommendations for chlamydia diagnostics and treatment. However, the survey identified NP deficits in screening and treatment practices for pregnant women. These findings are disturbing given the serious risks associated with failure to promptly diagnose and treat prenatal infections. The survey highlights the need for continuing professional education about chlamydia and other sexually transmitted infections.

Adolescent↗

IL-12 administered during Chlamydia psittaci lung infection in mice confers immediate and long-term protection and reduces macrophage inflammatory protein-2 level and neutrophil infiltration in lung tissue.

Protection against infections with the intracellular bacterium Chlamydia spp. requires Th1-polarized CD4+ T cell immunity. In BALB/c mouse lung infections, immediate innate and nascent Chlamydia-specific immune responses following intranasal inoculation of Chlamydia psittaci strain B577 were modulated by 7-day i.p. administration of murine rIL-12, the initiation cytokine for Th1 immunity. Treatment with IL-12 reduced the severity of chlamydial pneumonia, abolished mortality (37.5% in untreated mice), and significantly reduced numbers of chlamydial organisms in lungs. On day 4 after inoculation, the neutrophil:macrophage ratio in bronchointerstitial pneumonias was 1.96 in untreated mice and 0.51 in IL-12-treated mice. This immediate, IL-12-mediated shift in innate inflammatory phenotype was correlated with a significant reduction of lung concentrations of the neutrophil chemoattractant macrophage inflammatory protein (MIP)-2 (putative murine homologue of human IL-8), monocyte chemotactic protein-1, and TNF-alpha; and a reduction in MIP-1alpha and IFN-gamma, at high-dose infection only, and IL-12-independent IL-10 levels. Chlamydia-specific Ab titers and Ig isotype ratios indicated an IL-12-dependent Th1 shift. Recall responses of IL-12-primed mice to secondary chlamydial lung infection eliminated chlamydiae more effectively and generated a lung cytokine profile conducive to perpetuation of the Th1 memory population. These data support the hypothesis that genetic differences in endogenous IL-12 production and response pathways could determine disease outcomes characterized by poor chlamydial clearance and a purulent inflammatory infiltrate vs effective elimination of chlamydiae in a macrophage-dominated response.

Administration, Intranasal↗

Immune response to genital chlamydial infection and influence of Chlamydia pneumoniae (TWAR) antibodies.

Chlamydial IgG antibodies at a titre of at least 32 were found to occur at approximately the same frequency (76-88%) in three groups of patients who had been treated for genital chlamydial infection. Twenty-four patients who had recovered from acute salpingitis, however, had a higher geometric mean titre (GMT; 176) than 59 pregnant women (GMT 44) or 61 patients with uncomplicated genital chlamydial infection (GMT 57). The chlamydial antibody titres thus seemed to reflect the severity of inflammatory involvement. Antibodies to the new species Chlamydia pneumoniae (previously known as Chlamydia TWAR), did not influence the frequency or titre of antibodies to Chlamydia trachomatis, arguing against the possibility of cross-reactivity or shared antigens. There was assumed to be no cross-immunity, since patients with Chlamydia trachomatis infection did not have a lower frequency of antibodies to Chlamydia pneumoniae.

Adolescent↗

Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas.

BACKGROUND: Ocular adnexal lymphomas may be antigen-driven disorders; however, the source of the putative antigen or antigens is still unknown. Hence, we assessed whether Chlamydiae infection is associated with the development of ocular adnexal lymphomas. METHODS: The presence of Chlamydia psittaci, trachomatis, and pneumoniae DNA was investigated by polymerase chain reaction in 40 ocular adnexal lymphoma samples, 20 nonneoplastic orbital biopsies, 26 reactive lymphadenopathy samples, and peripheral blood mononuclear cells (PBMCs) from 21 lymphoma patients and 38 healthy individuals. Seven patients with chlamydia-positive PBMCs were treated with the antibiotic doxycycline, and objective response was assessed in four patients with measurable lymphoma lesions. Differences in Chlamydiae DNA detection between the case patients and the control subjects were analyzed using the Fisher exact test. All statistical tests were two-sided. RESULTS: Thirty-two of the 40 (80%) ocular adnexal lymphoma samples carried C. psittaci DNA, whereas all lymphoma samples were negative for C. trachomatis and C. pneumoniae. In contrast, none of the 20 nonneoplastic orbital biopsies (0% versus 80%; P<.001) and only three of 26 (12%) reactive lymphadenopathy samples (12% versus 80%; P<.001) carried the C. psittaci DNA. Nine of 21 (43%) patients with chlamydia-positive lymphomas carried C. psittaci DNA in their PBMCs, whereas none (0%) of the healthy PBMC donors carried C. psittaci DNA in their PBMCs (43% versus 0%; P<.001). One month after doxycycline treatment, chlamydial DNA was no longer detectable in the PBMCs of all seven treated patients, and objective response was observed in two of the four evaluable patients. CONCLUSION: Patients with ocular adnexal lymphoma had a high prevalence of C. psittaci infection in both tumor tissue and PBMCs. Persistent C. psittaci infection may contribute to the development of these lymphomas, as was also supported by the clinical responses observed in this study with C. psittaci-eradicating antibiotic therapy.

Adult↗

Chlamydia screening of youth and young adults in non-clinical settings throughout California.

BACKGROUND: Urine-based chlamydia tests enable screening in non-clinical settings. GOAL: The goal of this study was to determine the prevalence of chlamydia infection among high-risk youth and young adults in non-clinical settings. DESIGN: County sexually transmitted disease (STD) programs implemented chlamydia screening projects in non-clinical settings using nucleic acid amplification tests. Demographic and access to care data were collected. RESULTS: Overall, 16,279 female and male youth were screened for chlamydia in 24 counties throughout California. The 158 screening venues included 32 educational, 32 correctional, and 94 community-based settings. Chlamydia infection rates varied significantly by gender, age, and venue type. Among females, the highest prevalence was found in jail settings (14.6%), juvenile detention (13.0%), and alternative schools (10.0%). Among males, the highest prevalence was found in jail (7.9%) and juvenile detention (5.8%). Venue types that serve populations with poor access to care and high rates of infection were identified. CONCLUSIONS: Screening projects in non-clinical settings identify high-risk youth in need of STD care, improve access to STD screening and education, and foster local collaborations.

Adolescent↗

Chlamydia infections and heart disease linked through antigenic mimicry.

Chlamydia infections are epidemiologically linked to human heart disease. A peptide from the murine heart muscle-specific alpha myosin heavy chain that has sequence homology to the 60-kilodalton cysteine-rich outer membrane proteins of Chlamydia pneumoniae, C. psittaci, and C. trachomatis was shown to induce autoimmune inflammatory heart disease in mice. Injection of the homologous Chlamydia peptides into mice also induced perivascular inflammation, fibrotic changes, and blood vessel occlusion in the heart, as well as triggering T and B cell reactivity to the homologous endogenous heart muscle-specific peptide. Chlamydia DNA functioned as an adjuvant in the triggering of peptide-induced inflammatory heart disease. Infection with C. trachomatis led to the production of autoantibodies to heart muscle-specific epitopes. Thus, Chlamydia-mediated heart disease is induced by antigenic mimicry of a heart muscle-specific protein.

Adoptive Transfer↗

Analysis of the humoral immune response to Chlamydia outer membrane protein 2.

The humoral immune response to Chlamydia outer membrane protein 2 (Omp2) was studied. Omp2 is a highly genus-conserved structural protein of all Chlamydia species, containing a variable N-terminal fragment. To analyze where the immunogenic parts were localized, seven highly purified truncated fusion proteins constituting different regions of the protein were produced (Chlamydia pneumoniae-Omp2aa23-aa93, Chlamydia psittaci-Omp2aa23-aa94, and Chlamydia trachomatis-Omp2aa23-aa84, aa87-aa547, aa23-aa182, aa167-aa434, aa420-aa547). By an enzyme-linked immunosorbent assay with serologically defined patient sera, Omp2 was found to be a major immunogen of both C. pneumoniae and C. trachomatis infections (P < 0.0001). The humoral immune responses were not confined to any particular region of the Omp2 protein, and no species-specific anti-Omp2 immunoglobulins were detected.

Antibodies, Bacterial↗

Genomic relatedness of Chlamydia isolates determined by amplified fragment length polymorphism analysis.

The genomic relatedness of 19 Chlamydia pneumoniae isolates (17 from respiratory origin and 2 from atherosclerotic origin), 21 Chlamydia trachomatis isolates (all serovars from the human biovar, an isolate from the mouse biovar, and a porcine isolate), 6 Chlamydia psittaci isolates (5 avian isolates and 1 feline isolate), and 1 Chlamydia pecorum isolate was studied by analyzing genomic amplified fragment length polymorphism (AFLP) fingerprints. The AFLP procedure was adapted from a previously developed method for characterization of clinical C. trachomatis isolates. The fingerprints of all C. pneumoniae isolates were nearly identical, clustering together at a Dice similarity of 92.6% (+/- 1.6% standard deviation). The fingerprints of the C. trachomatis isolates of human, mouse, and swine origin were clearly distinct from each other. The fingerprints of the isolates from the human biovar could be divided into at least 12 different types when the presence or absence of specific bands was taken into account. The C. psittaci fingerprints could be divided into a parakeet, a pigeon, and a feline type. The fingerprint of C. pecorum was clearly distinct from all others. Cluster analysis of selected isolates from all species revealed groups other than those based on sequence data from single genes (in particular, omp1 and rRNA genes) but was in agreement with available DNA-DNA hybridization data. In conclusion, cluster analysis of AFLP fingerprints of representatives of all species provided suggestions for a grouping of chlamydiae based on the analysis of the whole genome. Furthermore, genomic AFLP analysis showed that the genome of C. pneumoniae is highly conserved and that no differences exist between isolates of respiratory and atherosclerotic origins.

Animals↗