Eylem Seç
The Role of Exosomes in Chlamydial Immunity
Başlık:
The Role of Exosomes in Chlamydial Immunity
Yazar:
Russell, Raedeen Sherilee, author.
ISBN:
9780355977080
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (187 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Francis O. Eko Committee members: Ernest Alema-Mensah; Joseph U. Igietseme; Michael D. Powell; Anisia Silva-Benitez.
Özet:
Exosomes are extracellular vesicles that package cellular components from donor cells and transport them to recipient cells. While there is mounting evidence of exosomes as immune modulators, their role in Chlamydia immunity is lacking. The aims of this study were to characterize Chlamydial infection-derived exosomes, assess their role in Chlamydial immunity, and explore their ability to confer protection in a murine model. Additionally, we wanted to assess National Health and Nutrition Examination Survey (NHANES) 2013--2014 to identify predictors of Chlamydial infection in Lab-reported and Self-reported data. We hypothesized that Chlamydia infection-derived exosomes (IDEX) possess immunomodulatory properties that can prime the innate immune system to facilitate timely adaptive response.
To answer our aim, we isolated exosomes from Chlamydia-infected epithelial cells and characterized them using NanoSight and Western Blot analysis. We further assessed the consequence of exosomes on antigen presenting cells. Lastly, we immunized mice directly with IDEX along with Vibrio cholera ghost (VCG) as an adjuvant, or by adoptive transfer of Jaws-II dendritic cells (DC) pulsed with IDEX, IDEX+ ultra-violet irradiated Chlamydia elementary body (UV-EB) or UV-EB only. We later evaluated their ability to confer protection by analyzing collected serum samples, vaginal lavages, vaginal swabs and spleens.
We showed that IDEX packaged both host and microbial factors that can activate the maturation of DCs. Moreover, we also showed that IDEX activate NF-kappaB which in turn activates the secretion of cytokines from DCs. Immunization with either IDEX+VCG or by adoptive transfer revealed that exosomes can induce proliferation in naive and immune T-cells, and increase the secretion of IFN-gamma, a Th1 type cytokine but not IL-4, a Th2 type cytokine. Immunization also induced the secretion of IgG and IgG2c in serum, IgA in vaginal lavage after day 7 of challenge, and it reduced bacterial shedding in the genital tract of mice.
Taken together, these studies indicate that infection-derived exosomes possess immunomodulatory properties, they can prime the innate immune response to facilitate timely adaptive immunity and they can be used as vaccine antigens to protect against Chlamydia infection. Our database analysis of NHANES 2013--2014 indicates that age is the strongest predictor of Chlamydial infection in both Lab-reported and Self-reported data, with adolescents 25 years and younger at higher risk for infection with Chlamydia. We therefore suggest the development of an anti-Chlamydial vaccine, using exosomes as a novel vaccine strategy, and specifically targeting adolescents 25 years and younger.
Notlar:
School code: 1943
Tüzel Kişi Ek Girişi:
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(680971.1) | 680971-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
On Order
Liste seç
Bunu varsayılan liste yap.
Öğeler başarıyla eklendi
Öğeler eklenirken hata oldu. Lütfen tekrar deneyiniz.
:
Select An Item
Data usage warning: You will receive one text message for each title you selected.
Standard text messaging rates apply.