Up‐regulation of microsphere transport across the follicle‐associated epithelium of Peyer's patch by exposure to Streptococcus pneumoniae R36a

Abstract

Transport of antigens through the follicle-associated epithelium (FAE) of Peyer's patch (PP) is the critical first step in the induction of mucosal immune responses. We have previously described that short-term exposure to Streptococcus pneumoniae R36a induced dramatic morphological alterations of the FAE in rabbit PP. These results prompted us to investigate whether the pneumococci-induced modifications were accompanied by enhanced ability of the FAE to transport antigens. We addressed this problem by evaluating the ability of the FAE to bind, internalize, and transport fluorescent polystyrene microparticles, highly specific to rabbit M cells, after exposure to S. pneumoniae. Quantitative study revealed a marked increase in the number of microspheres in PP tissues exposed to S. pneumoniae compared to tissues exposed to either phosphate-buffered saline or Escherichia coli DH5alpha as controls. No sign of bacterially induced damage to the epithelial barrier was observed. Further confocal microscopy analysis of the FAE surface showed that a significant increase in the number of cells that showed both morphological and functional features of M cells took place within pneumococci-treated PP tissues. These data provide the first direct evidence that the FAE-specific antigen sampling function may be manipulated to improve antigen and drug delivery to the intestinal immune system.

Yersinia pseudotuberculosis induces transcytosis of nanoparticles across human intestinal villus epithelium via invasin-dependent macropinocytosis

“…33,36 Moreover, previous in vivo studies in rodents demonstrated an increased transcytosis across FAE after microbial challenge, explained either by induction of the M cell phenotype and/or an increased transport rate in already present M cells. 46,47 In the present study we showed that inv þ Y. pseudotuberculosis rapidly altered the transcytosis pattern of Caco-2 monolayers in complete absence of lymphocytes or lymphocyte-derived products. Moreover, we verified this Significantly changed compared to control (Po0.001).…”

“…38 The increase was detectible already after 2 h of exposure to the bacteria, which is compatible with earlier reports in rodents, where an increased number of M cells has been detected in ileal loops already 1 h after inoculation with Streptococcus pneumoniae R36a. 47 Our investigation was focused on the cellular responses in nonphagocytic cells after exposure to Y. pseudotuberculosis, but it is possible that an increased transcytosis also can be seen after exposure to other enteroinvasive bacteria. In support of this notion, Lyons et al recently showed that Salmonella typhimurium transcytoses flagellin via a SPI2-mediated vesicular transport across polarized epithelial cells.…”

Role of Commensal Bacteria in Development of Gut-Associated Lymphoid Tissues and Preimmune Antibody Repertoire

“…Therefore, we suggest that one role of B. fragilis may be to enhance uptake of B. subtilis. Consistent with this idea, Meynell et al (34) observed an increase in transport of latex microspheres by rabbit Peyer's patch M cells when exposed to Streptococcus pneumoniae, but not to E. coli. We suggest that if B. subtilis is taken up by M cells efficiently, it alone can induce GALT development and somatic diversification of Ig genes.…”

Intestinal villous M cells: An antigen entry site in the mucosal epithelium

“…Our findings presented here, however, challenge this common assumption by providing evidence that M cells can be developed in villous epithelium in the absence of the FAE thought to be necessary to their development in the organized mucosal lymphoid tissue. The diverse cellular phenotypes in the intestinal epithelium arise from crypt stem cells whose differentiation pathways can be modified by endogenous and exogenous influences (33)(34)(35)(36)(37). A previous study (34) demonstrated that Streptococcus pneumoniae-treated FAE tissues showed a marked increase in both IEL and epithelial cells with morphological and functional features of M cells.…”