Stimulated peripheral blood mononuclear cells from chlamydia-infected women release predominantly Th1-polarizing cytokines

Jordan, Stephen J.; Bakshi, Rakesh K.; Brown, Laura L.; Chi, Xiaofei; Geisler, William M.

doi:10.1016/j.cyto.2018.06.017

Cited by 6 publications

(4 citation statements)

References 16 publications

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“…The results from this work helped enable a better understanding of mitochondrial damage and cell heterogeneity (Kummer and Wilichowski 2018). LCM has played a role in single-inclusion level by isolating Chlamydia trachomatis-infected cells to study the generation of microbiological clones of C. trachomatis, and molecular assay tests to the isolated chlamydia cells to study cell features (Jordana et al 2016).…”

Section: Laser and Vacuum Microdissectionmentioning

confidence: 99%

Technologies for Single-Cell Printing and Patterning

Ambhorkar

Sakr

Kumar

et al. 2021

Handbook of Single-Cell Technologies

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Printing single cells after isolating them from heterogeneous cell populations has the potential to reveal several new insights into cell behavior, therapeutics, and precision medicine. Since studies conducted on individual cells are independent of background noise that results from other cells present in the vicinity as well as intercellular phenotypic heterogeneity, they can provide an accurate characterization of tissue microenvironments such as multiclonal tumors while allowing single-cell genome/proteome analysis. Additionally, the ability to print at the Pranav Ambhorkar and Mahmoud Ahmed Sakr contributed equally with all other contributors.

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Section: Laser and Vacuum Microdissectionmentioning

confidence: 99%

Technologies for Single-Cell Printing and Patterning

Ambhorkar

Sakr

Kumar

et al. 2021

Handbook of Single-Cell Technologies

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“…In a recent proof-of-principle vaccine study using TriAdj-adjuvanted UV-inactivated Cs as the vaccine, we demonstrated that this proof-of-principle vaccine induced a robust CD4 IFN-γ (=T-helper 1, Th1) response which is considered the mechanism of protection for various intracellular bacteria, including Ct, as reviewed in [5]. This Th1 response has been shown to be critical in the anti-Ct response [5,[30][31][32][33]. In addition, upon challenge with Cs, our TriAdj-adjuvanted UV-Cs vaccine candidate reduced the genital Cs load compared to unvaccinated pigs, demonstrating vaccine efficacy.…”

Section: Introductionmentioning

confidence: 95%

A TriAdj-Adjuvanted Chlamydia trachomatis CPAF Protein Vaccine Is Highly Immunogenic in Pigs

Proctor,

Stadler,

Cortes

et al. 2024

Vaccines

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Chlamydia trachomatis (Ct) infections are the most common sexually transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs, as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we used the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial-protease-like activity factor (CPAF) protein. We tested two weekly administration options—twice intranasal (IN) followed by twice intramuscular (IM) and twice IM followed by twice IN. We assessed the humoral immune response in both serum using CPAF-specific IgG (including antibody avidity determination) and also in cervical and rectal swabs using CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed following in vitro CPAF restimulation via IFN-γ and IL-17 ELISpots, as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity, as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response. Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response with CD4 T cells. In IM/IN-vaccinated pigs, these cells also significantly downregulated their CCR7 expression, a sign of differentiation into peripheral-tissue-homing effector/memory cells. Conclusively, this study demonstrates the strong immunogenicity of the IM/IN-administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test the vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates the suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.

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“…CD4 T cells in human Chlamydia infection secrete significant levels of IFN-γ [27,28]. Similarly, CD4 T cells recovered from the FRT of Chlamydia-infected mice secrete IFN-γ [19], while mice genetically deficient in IFN-γ or IFN-γR suffer from an overwhelming systemic infection [29,30].…”

Section: Introductionmentioning

confidence: 99%

Elimination of Chlamydia muridarum from the female reproductive tract is IL-12p40 dependent, but independent of Th1 and Th2 cells

Rixon,

Fong,

Morris

et al. 2024

PLoS Pathog

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Chlamydia vaccine approaches aspire to induce Th1 cells for optimal protection, despite the fact that there is no direct evidence demonstrating Th1-mediated Chlamydia clearance from the female reproductive tract (FRT). We recently reported that T-bet-deficient mice can resolve primary Chlamydia infection normally, undermining the potentially protective role of Th1 cells in Chlamydia immunity. Here, we show that T-bet-deficient mice develop robust Th17 responses and that mice deficient in Th17 cells exhibit delayed bacterial clearance, demonstrating that Chlamydia-specific Th17 cells represent an underappreciated protective population. Additionally, Th2-deficient mice competently clear cervicovaginal infection. Furthermore, we show that sensing of IFN-γ by non-hematopoietic cells is essential for Chlamydia immunity, yet bacterial clearance in the FRT does not require IFN-γ secretion by CD4 T cells. Despite the fact that Th1 cells are not necessary for Chlamydia clearance, protective immunity to Chlamydia is still dependent on MHC class-II-restricted CD4 T cells and IL-12p40. Together, these data point to IL-12p40-dependent CD4 effector maturation as essential for Chlamydia immunity, and Th17 cells to a lesser extent, yet neither Th1 nor Th2 cell development is critical. Future Chlamydia vaccination efforts will be more effective if they focus on induction of this protective CD4 T cell population.

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Stimulated peripheral blood mononuclear cells from chlamydia-infected women release predominantly Th1-polarizing cytokines

Cited by 6 publications

References 16 publications

Technologies for Single-Cell Printing and Patterning

Technologies for Single-Cell Printing and Patterning

A TriAdj-Adjuvanted Chlamydia trachomatis CPAF Protein Vaccine Is Highly Immunogenic in Pigs

Elimination of Chlamydia muridarum from the female reproductive tract is IL-12p40 dependent, but independent of Th1 and Th2 cells

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