A Population of Langerin-Positive Dendritic Cells in Murine Peyer's Patches Involved in Sampling β-Glucan Microparticles

The Ohio State University, United States of America
PLoS ONE (Impact Factor: 3.23). 03/2014; 9(3):e91002. DOI: 10.1371/journal.pone.0091002
Source: PubMed


Glucan particles (GPs) are 2-4 μm hollow, porous shells composed of 1,3-β-D-glucan that have been effectively used for oral targeted-delivery of a wide range of payloads, including small molecules, siRNA, DNA, and protein antigens. While it has been demonstrated that the transepithelial transport of GPs is mediated by Peyer's patch M cells, the fate of the GPs once within gut-associated lymphoid tissue (GALT) is not known. Here we report that fluorescently labeled GPs administered to mice by gavage accumulate in CD11c+ DCs situated in Peyer's patch sub-epithelial dome (SED) regions. GPs appeared in DCs within minutes after gavage and remained within the SED for days afterwards. The co-administration or sequential administration of GPs with differentially labeled GPs or poly(lactic-co-glycolic acid) nanoparticles demonstrated that the SED DC subpopulation in question was capable of internalizing particles of different sizes and material compositions. Phenotypic analysis identified the GP-containing DCs as being CD8α- and CD11blo/-, suggesting they are the so-called myeloid and/or double negative (DN) subset(s) of PP DCs. A survey of C-type lectin receptors (CLRs) known to be expressed by leukocytes within the intestinal mucosa revealed that GP-containing SED DCs were positive for Langerin (CD207), a CLR with specificity for β-D-glucan and that has been shown to mediate the internalization of a wide range of microbial pathogens, including bacteria, viruses and fungi. The presence of Langerin+ DCs in the SED as determined by immunofluorescence was confirmed using Langerin E-GFP transgenic mice. In summary, our results demonstrate that following M cell-mediated transepithelial transport, GPs (and other micro/nanoparticles) are sampled by a population of SED DCs distinguished from other Peyer's patch DC subsets by their expression of Langerin. Future studies will be aimed at defining the role of Langerin in antigen sampling and antigen presentation within the context of the GALT.

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Available from: Gary R Ostroff, Jul 16, 2014
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    • "6 specific secretory IgA in intestinal fluids [22]. This local immune response is obtained via the transepithelial transport of GPs by Peyer's patch M cells [11] [22] [24], resulting in the accumulation of GPs in CD11c + phagocytes situated in the Peyer's patch sub-epithelial dome (SED) regions [11]. However, M cells represent only a minor cell population in the intestinal tract and a huge amount of particles is necessary to induce immunity. "
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