Abstract
The female reproductive tract (FRT) includes the oviducts (fallopian tubes), uterus, cervix and vagina. A layer of columnar epithelium separates the endocervix and uterus from the outside environment, while the vagina is lined with stratified squamous epithelium. The mucosa of the FRT is exposed to antigens originating from microflora, and occasionally from infectious microorganisms. Whether epithelial cells (ECs) of the FRT take up (sample) the lumen antigens is not known. To address this question, we examined the uptake of 20–40 nm nanoparticles (NPs) applied vaginally to mice which were not treated with hormones, epithelial disruptors, or adjuvants. We found that 20 and 40 nm NPs are quickly internalized by ECs of the upper FRT and within one hour could be observed in the lymphatic ducts that drain the FRT, as well as in the ileac lymph nodes (ILNs) and the mesenteric lymph nodes (MLNs). Chicken ovalbumin (Ova) conjugated to 20 nm NPs (NP-Ova) when administered vaginally reaches the internal milieu in an immunologically relevant form; thus vaginal immunization of mice with NP-Ova induces systemic IgG to Ova antigen. Most importantly, vaginal immunization primes the intestinal mucosa for secretion of sIgA. Sub-cutaneous (s.c) boosting immunization with Ova in complete Freund's adjuvant (CFA) further elevates the systemic (IgG1 and IgG2c) as well as mucosal (IgG1 and sIgA) antibody titers. These findings suggest that the modes of antigen uptake at mucosal surfaces and pathways of antigen transport are more complex than previously appreciated.
Highlights
The mucosa of the female reproductive tract (FRT) is a major site of entry and transmission of sexually transmitted pathogens such as Chlamydia, Gonorrhea, human immunodeficiency virus (HIV), human papillomavirus (HPV), etc
In initial experiments we examined whether epithelial cells (ECs) of the FRT can internalize NPs administered in the lumen without treatment with progesterone, EC disruptors, or mucosal adjuvants
Immunization via the FRT mucosa is the preferable route for induction of local immune responses which are essential for prevention of sexually-transmitted infections (STIs) and for limiting disease severity [32, 33, 34]
Summary
The mucosa of the FRT is a major site of entry and transmission of sexually transmitted pathogens such as Chlamydia, Gonorrhea, human immunodeficiency virus (HIV), human papillomavirus (HPV), etc. To enhance antigen entry in the FRT mucosa without the use of adjuvants, in many studies pre-treatment of animals with progesterone, followed by mechanical or chemical disruption of the FRT epithelium is commonly practiced These approaches were used for vaginal delivery of PLGA NPs [28], virus-like particles (VLP), HPV [12], and quantum dots (,10 nm) [29]. We show that intra-vaginal immunization of mice with Ova-conjugated 20 nm NPs, in combination with a s.c. boost, induces systemic as well as mucosal antibodies In these studies animals were given no progesterone, the epithelium was not disrupted by any means, and no adjuvants were used, indicating that the FRT mucosa, much like the mucosa of the small intestine, has mechanisms by which antigens from the FRT lumen are internalized and transported to the internal milieu. Our findings have implications for understanding the biology of the FRT, as well as for development of mucosal vaccines to target STIs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
