Browsing by Author "Nagamatsu, Takeshi"

Filter results by typing the first few letters
Now showing 1 - 3 of 3
  • Thumbnail Image
    ItemOpen Access
    Chlamydia trachomatis immune evasion via downregulation of MHC class I surface expression involves direct and indirect mechanisms.
    (Infectious diseases in obstetrics and gynecology, 2011-01) Ibana, Joyce A; Schust, Danny J; Sugimoto, Jun; Nagamatsu, Takeshi; Greene, Sheila J; Quayle, Alison J
    Genital C. trachomatis infections typically last for many months in women. This has been attributed to several strategies by which C. trachomatis evades immune detection, including well-described methods by which C. trachomatis decreases the cell surface expression of the antigen presenting molecules major histocompatibility complex (MHC) class I, MHC class II, and CD1d in infected genital epithelial cells. We have harnessed new methods that allow for separate evaluation of infected and uninfected cells within a mixed population of chlamydia-infected endocervical epithelial cells to demonstrate that MHC class I downregulation in the presence of C. trachomatis is mediated by direct and indirect (soluble) factors. Such indirect mechanisms may aid in priming surrounding cells for more rapid immune evasion upon pathogen entry and help promote unfettered spread of C. trachomatis genital infections.
  • Thumbnail Image
    ItemOpen Access
    Chlamydia trachomatis-infected cells and uninfected-bystander cells exhibit diametrically opposed responses to interferon gamma.
    (Scientific reports, 2018-05) Ibana, Joyce A; Sherchand, Shardulendra P; Fontanilla, Francis L; Nagamatsu, Takeshi; Schust, Danny J; Quayle, Alison J; Aiyar, Ashok
    The intracellular bacterial pathogen, Chlamydia trachomatis, is a tryptophan auxotroph. Therefore, induction of the host tryptophan catabolizing enzyme, indoleamine-2,3-dioxgenase-1 (IDO1), by interferon gamma (IFNγ) is one of the primary protective responses against chlamydial infection. However, despite the presence of a robust IFNγ response, active and replicating C. trachomatis can be detected in cervical secretions of women. We hypothesized that a primary C. trachomatis infection may evade the IFNγ response, and that the protective effect of this cytokine results from its activation of tryptophan catabolism in bystander cells. To test this hypothesis, we developed a novel method to separate a pool of cells exposed to C. trachomatis into pure populations of live infected and bystander cells and applied this technique to distinguish between the effects of IFNγ on infected and bystander cells. Our findings revealed that the protective induction of IDO1 is suppressed specifically within primary infected cells because Chlamydia attenuates the nuclear import of activated STAT1 following IFNγ exposure, without affecting STAT1 levels or phosphorylation. Critically, the IFNγ-mediated induction of IDO1 activity is unhindered in bystander cells. Therefore, the IDO1-mediated tryptophan catabolism is functional in these cells, transforming these bystander cells into inhospitable hosts for a secondary C. trachomatis infection.
  • Thumbnail Image
    ItemOpen Access
    Enhanced HIF2α expression during human trophoblast differentiation into syncytiotrophoblast suppresses transcription of placental growth factor.
    (Scientific reports, 2017-09) Fujii, Tatsuya; Nagamatsu, Takeshi; Morita, Kazuki; Schust, Danny J; Iriyama, Takayuki; Komatsu, Atsushi; Osuga, Yutaka; Fujii, Tomoyuki
    Placental growth factor (PlGF), abundantly produced from trophoblasts is involved in placental angiogenesis. The regulatory mechanism of its expression is poorly understood. Hypoxia inducible factors (HIFs) are centrally involved in the modulation of cellular function in response to low oxygen conditions. This study aimed to clarify HIF1α and HIF2α expression patterns during cytotrophoblast differentiation into syncytiotrophoblast and the impact of any changes on PlGF expression. HIF proteins were induced remarkably under low oxygen condition (2%). HIF1α expression decreased and HIF2α expression increased when syncytialization of cultured cytotrophoblasts is progressed. Those expression changes of HIF proteins in the process of in-vitro syncytialization was congruent with the immunohistochemical findings in preeclamptic placenta as well as uncomplicated placenta. Low oxygen condition was also associated with reduced PlGF production in syncytializing primary cells and BeWo choriocarcinoma cells. Small interfering RNA-mediated HIF2α knockdown in BeWo cells abrogated hypoxia-associated decreases in PlGF secretion; HIF1α silencing had no significant effect on PlGF secretion. In summary, HIF2α, rather than HIF1α, is most affected by reduced oxygen level during syncytialization and increases in HIF2α trigger a reduction of PlGF production. Our findings suggest new and important connections between HIF proteins and PlGF pathways in the regulation of placental angiogenesis.