M-cells contribute to the entry of an oral vaccine but are not essential for the subsequent induction of protective immunity against Francisella tularensis

Aimee L. Cunningham, M. Neal Guentzel, Jieh Juen Yu, Chiung Yu Hung, Thomas G. Forsthuber, Christopher S. Navara, Hideo Yagita, Ifor R. Williams, Karl E. Klose, Tonyia Eaves-Pyles, Bernard P. Arulanandam

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3 Scopus citations

Abstract

M-cells (microfold cells) are thought to be a primary conduit of intestinal antigen trafficking. Using an established neutralizing anti-RANKL (Receptor Activator of NF-κB Ligand) antibody treatment to transiently deplete M-cells in vivo, we sought to determine whether intestinal M-cells were required for the effective induction of protective immunity following oral vaccination with ΔiglB (a defined live attenuated Francisella novicida mutant). M-cell depleted, ΔiglB-vaccinated mice exhibited increased (but not significant) morbidity and mortality following a subsequent homotypic or heterotypic pulmonary F. tularensis challenge. No significant differences in splenic IFN-ã, IL-2, or IL-17 or serum antibody (IgG1, IgG2a, IgA) production were observed compared to non-depleted, ΔiglB-vaccinated animals suggesting complementary mechanisms for ΔiglB entry. Thus, we examined other possible routes of gastrointestinal antigen sampling following oral vaccination and found that ΔiglB co-localized to villus goblet cells and enterocytes. These results provide insight into the role of M-cells and complementary pathways in intestinal antigen trafficking that may be involved in the generation of optimal immunity following oral vaccination.

Original languageEnglish (US)
Article numbere0153402
JournalPLoS One
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2016

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cunningham, A. L., Guentzel, M. N., Yu, J. J., Hung, C. Y., Forsthuber, T. G., Navara, C. S., Yagita, H., Williams, I. R., Klose, K. E., Eaves-Pyles, T., & Arulanandam, B. P. (2016). M-cells contribute to the entry of an oral vaccine but are not essential for the subsequent induction of protective immunity against Francisella tularensis. PLoS One, 11(4), [e0153402]. https://doi.org/10.1371/journal.pone.0153402