PMID- 25490456 OWN - NLM STAT- MEDLINE DCOM- 20160126 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 12 DP - 2014 TI - Protein-coated nanoparticles are internalized by the epithelial cells of the female reproductive tract and induce systemic and mucosal immune responses. PG - e114601 LID - 10.1371/journal.pone.0114601 [doi] LID - e114601 AB - 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. FAU - Howe, Savannah E AU - Howe SE AD - Department of Microbiology, Southern Illinois University, Carbondale, Illinois, United States of America. FAU - Konjufca, Vjollca H AU - Konjufca VH AD - Department of Microbiology, Southern Illinois University, Carbondale, Illinois, United States of America. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141209 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antigens) RN - 0 (Immunoglobulin G) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Animals MH - Antigens/immunology/*metabolism MH - Biological Transport MH - Epithelial Cells/immunology/*metabolism MH - Female MH - Immunity, Mucosal MH - Immunization/methods MH - Immunoglobulin G/blood MH - Lymph Nodes/immunology/physiology MH - Mice MH - Mice, Inbred C57BL MH - Nanoparticles/*analysis MH - Ovalbumin/immunology MH - *Vaginal Absorption PMC - PMC4260873 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/12/10 06:00 MHDA- 2016/01/27 06:00 PMCR- 2014/12/09 CRDT- 2014/12/10 06:00 PHST- 2014/05/16 00:00 [received] PHST- 2014/11/11 00:00 [accepted] PHST- 2014/12/10 06:00 [entrez] PHST- 2014/12/10 06:00 [pubmed] PHST- 2016/01/27 06:00 [medline] PHST- 2014/12/09 00:00 [pmc-release] AID - PONE-D-14-21968 [pii] AID - 10.1371/journal.pone.0114601 [doi] PST - epublish SO - PLoS One. 2014 Dec 9;9(12):e114601. doi: 10.1371/journal.pone.0114601. eCollection 2014.