Slow cycling intestinal stem cell and Paneth cell responses to Trichinella spiralis infection

Parasitol Int. 2020 Feb:74:101923. doi: 10.1016/j.parint.2019.05.001. Epub 2019 May 2.

Abstract

There is limited information regarding responses by slow cycling stem cells during T. spiralis-induced T-cell mediated intestinal inflammation and how such responses may relate to those of Paneth cells. Transgenic mice, in which doxycycline induces expression of histone 2B (H2B)-green fluorescent protein (GFP), were used. Following discontinuation of doxycycline ("chase" period), retention of H2B-GFP enabled the identification of slow cycling stem cells and long-lived Paneth cells. Inflammation in the small intestine (SI) was induced by oral administration of T. spiralis muscle larvae. Epithelial retention of H2B-GFP per crypt cell position (cp) was studied following immunohistochemistry and using the Score and Wincrypts program. Compared to non-infected controls, there was significant reduction in the number of H2B-GFP-retaining stem cells in T. spiralis-infected small intestines. H2B-GFP-retaining stem cells peaked at around cp 4 in control sections, but smaller peaks at higher cell positions (>10) were seen in sections of inflamed small intestines. In the latter, there was a significant increase in the total number of Paneth cells, with significant reduction in H2B-GFP-retaining Paneth cells, but a marked increase in unlabelled (H2B-GFP-negative) Paneth cells. In conclusion, following T. spiralis-infection, putative slow cycling stem cell numbers were reduced. A marked increase in newly generated Paneth cells at the crypt base led to higher cell positions of the remaining slow cycling stem cells.

Keywords: Paneth cells; Stem cells; Trichinella spiralis.

MeSH terms

  • Animals
  • Cell Cycle
  • Female
  • Green Fluorescent Proteins / genetics
  • Histones / genetics
  • Immunohistochemistry
  • Intestine, Small / cytology*
  • Intestine, Small / immunology
  • Intestine, Small / parasitology
  • Male
  • Mice
  • Mice, Transgenic
  • Paneth Cells / immunology
  • Paneth Cells / parasitology*
  • Stem Cells / immunology
  • Stem Cells / parasitology*
  • Trichinella spiralis
  • Trichinellosis / immunology*

Substances

  • Histones
  • Green Fluorescent Proteins