A primary Chlamydia trachomatis genital infection of Rhesus macaques identifies new immunodominant B-cell antigens
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PROVIDER: PRJNA635077 | ENA |
REPOSITORIES: ENA
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Project description:To identify immunodominant antigens that elicit a humoral immune response following a primary genital infection, rhesus monkeys were inoculated cervically with Chlamydia trachomatis serovar D. Serum samples were collected and probed with a protein microarray expressing 864/894 (96.4%) of the open reading frames of the C. trachomatis serovar D genome. The antibody response was analyzed in 72 serum samples from 12 inoculated monkeys. The following criteria were utilized to identify immunodominant antigens: proteins found to be recognized by at least 75% (9/12) of the infected monkeys with at least 15% elevations in normalized signal intensity from week 0 to week 8 post infection. All infected monkeys developed Chlamydia specific serum antibodies. Eight proteins satisfied the selection criteria for immunodominant antigens: CT242 (OmpH-like protein), CT541 (mip), CT681 (ompA), CT381 (artJ), CT443 (omcB), CT119 (incA), CT486 (fliY), and CT110 (groEL). Of these, three antigens, CT119, CT486 and CT381, were not previously identified as immunodominant antigens using non-human primate sera. In conclusion, these immunodominant antigens can now be tested for their ability to identify individuals with a primary C. trachomatis genital infection and to design a vaccine strategy to protect against a primary infection with this pathogen.
2020-05-27 | GSE151183 | GEO
Project description:Chlamydia trachomatis is an obligate intracellular Gram-negative bacterium that frequently causes an asymptomatic genital tract infection, gradually cleared by host immunity Transcriptome profiles were made of endometrial tissue from women with or without genital tract C. trachomatis infection, to characterize host responses to infection. Profiles showed that infection polarized host defense toward Type 2 immune responses. Responses included fibrin deposition, enhanced wound repair, and tissue remodeling. Trans-cervical endometrial biopsy specimens were collected from 10 women with no identified upper or lower genital tract infection and 12 women with C. trachomatis endometrial infection.
2013-03-01 | E-GEOD-41075 | biostudies-arrayexpress
Project description:Chlamydia trachomatis is an obligate intracellular Gram-negative bacterium that frequently causes an asymptomatic genital tract infection, gradually cleared by host immunity Transcriptome profiles were made of endometrial tissue from women with or without genital tract C. trachomatis infection, to characterize host responses to infection. Profiles showed that infection polarized host defense toward Type 2 immune responses. Responses included fibrin deposition, enhanced wound repair, and tissue remodeling.
2013-03-01 | GSE41075 | GEO
Project description:To identify immunodominant antigens that elicit a humoral immune response following a primary and a secondary genital infection, rhesus monkeys were inoculated cervically with Chlamydia trachomatis serovar D. Serum samples were collected and probed with a protein microarray expressing 864/894 (96.4%) of the open reading frames of the C. trachomatis serovar D genome. The antibody response to the primary infection was analyzed in 72 serum samples from 12 inoculated monkeys. The following criteria were utilized to identify immunodominant antigens: proteins found to be recognized by at least 75% (9/12) of the infected monkeys with at least 15% elevations in signal intensity from week 0 to week 8 post infection. All infected monkeys developed Chlamydia specific serum antibodies. Eight proteins satisfied the selection criteria for immunodominant antigens: CT242 (OmpH-like protein), CT541 (mip), CT681 (ompA), CT381 (artJ), CT443 (omcB), CT119 (incA), CT486 (fliY), and CT110 (groEL). Of these, three antigens, CT119, CT486 and CT381, were not previously identified as immunodominant antigens using non-human primate sera. Following the secondary infection, the antibody responses to the eight immunodominant antigens were analyzed and found to be quite different in intensity and duration to the primary infection. In conclusion, these eight immunodominant antigens can now be tested for their ability to identify individuals with a primary C. trachomatis genital infection and to design vaccine strategies to protect against a primary infection with this pathogen.
| S-EPMC8061917 | biostudies-literature
Project description:By comprehensive quantitative proteome analysis we characterize the three growth forms elementary body (EB), reticulate body (RB) and aberrant reticulate body (ARB) of Chlamydia trachomatis genital strain D/UW-3/CX
2017-01-04 | PXD003883 | Pride
Project description:Introduction Chlamydia trachomatis (C. trachomatis) is a Gram-negative bacterium and a common human pathogen. The World Health Organization (WHO) estimates that over 130 million people are infected with C. trachomatis globally each year and with increasing incidence. C. trachomatis causes long-lasting and recurrent infections that over time induce severe tissue damage in the female genital tract that can lead to ectopic pregnancy and infertility. Thus, the human immune system fails to control and eradicate C. trachomatis during primary infection and fails to develop protective immunity against secondary infections. In vivo infection models, using complement knock out mice, suggest that the complement system is critically involved in both anti-chlamydial immunity and infection-induced pathology. To increase our understanding of complement-mediated immunity against C. trachomatis we analyzed global complement deposition on serum-incubated C. trachomatis by mass spectrometry. Methods Purified C. trachomatis was incubated in seronegative normal human serum (NHS) or heat-inactivated normal human serum (HI-NHS) for 30 min, thoroughly washed, and processed for mass spectrometry. All samples were lysed, reduced and alkylated and digested with trypsin. Some samples were chemically modified to acetylate free amino groups (N-terminal and lysine amino groups) before trypsin digestion. Peptides were analyzed on a UltimateTM 3500 RSLCnano coupled to a Q Exactive HF-X mass spectrometer. Raw data files were searched against the Uniprot human reference proteome using MaxQuant. Results We demonstrate that C. trachomatis elicits potent complement activation demonstrated by deposition of both early and late complement factors together with several complement regulators. We further demonstrate proteolytically processing of complement C3b to “inactive” C3 cleavage fragments. Conclusion We demonstrate the deposition of several novel complement-associated proteins and -cleavage fragments on the surface of C. trachomatis.
2020-11-23 | PXD019393 | Pride
Project description:Memory antigen-specific CD4+ T cells against Chlamydia trachomatis are necessary for protection against secondary genital tract infection. While it is known that naïve antigen-specific CD4+ T cells can traffic to the genital tract in an antigen-specific manner, these T cells are not protective during primary infection. Here, we sought to compare the differences between memory and naïve antigen-specific CD4+ T cells in the same mouse following secondary infection using transgenic CD4+ T cells (NR1 T cells). Using RNA sequencing, we found that there were subtle but distinct differences between these two T cell populations. Naïve NR1 T cells significantly upregulated cell cycle genes and were more proliferative than memory NR1 T cells in the draining lymph node. In contrast, memory NR1 T cells were more activated than naïve NR1 T cells and were enriched in the genital tract. Together, our data provide insight into the differences between memory and naïve antigen-specific CD4+ T cells during C. trachomatis infection.
2020-05-01 | GSE146265 | GEO
Project description:Rhesus macaques vaccinated by rhesus cytomegalovirus vectors expressing simian immunodeficiency virus proteins (RhCMV/SIV) activate gene expression signature associated with IL15. To examine the gene expression signature activated by IL15, we performed longitudinal examinations of rhesus macaques during IL15 treament.
2021-06-28 | GSE160577 | GEO
Project description:To investigate the role of cell type-intrinsic gene expression to fibrotic sequelae of Chlamydia trachomatis (Ct) infection of the upper female genital tract, we compared the transcriptomic response of primary human endocervical epithelial cells (HCECs, see GSE198272) to that in vaginal epithelial cells (HVEs).
2023-09-27 | GSE228774 | GEO
Project description:The cervix and/or fallopian tubes of pigtailed macaques were experimentally infected with Chlamydia trachomatis. Their sera were collected at varying time points and screened for identification of immunodominant antigens using a whole-genome protein microarray. The effect of doxycycline treatment on the antibody response generated in these macaques was also investigated. Twenty-five female macaques were infected with C. trachomatis serovars D or E in the cervix and/or fallopian tubes. Bloods were collected at baseline and at various intervals after challenge. Serum samples were tested for antibodies using a C. trachomatis serovar D protein microarray. Twenty chlamydial antigens reacted with sera from at least 68% (17/25) of the macaques. In addition to some well-known chlamydial antigens, nine different proteins, not previously recognized as immunodominant, including four hypothetical proteins (CT005, CT066, CT360 and CT578), were identified. Monkeys infected in the fallopian tubes developed a more robust antibody response than animals inoculated in the cervix. Treatment with doxycycline significantly decreased Chlamydia-specific antibody levels. In summary, using protein microarray serum samples from experimentally infected pigtailed macaques were screened for immunodominant chlamydial antigens. These antigens can now be tested in animal models for their ability to protect and as markers of disease progression.Biological significanceThis is the first time that Chlamydia trachomatis immunodominant antigens have been identified in pigtailed macaques following a uterine cervix or a fallopian tubes infection. These immunodominant antigens can now be used to vaccinate non-human primates and determine their ability to protect against a C. trachomatis genital infection. Proteins that are protective can subsequently be tested in humans. Amongst the immunodominant antigens some were predominantly recognized by sera from macaques inoculated in the fallopian tubes rather than in the cervix and therefore, may be markers for upper genital tract pathology. In addition, treatment with doxycycline following infection significantly decreased Chlamydia-specific antibody levels. This information can be used to evaluate the efficacy of antibiotic treatment and potentially susceptibility to reinfection.
| S-EPMC4112733 | biostudies-literature