Helminth-induced reprogramming of the stem cell compartment inhibits type 2 immunity

Area of Science:

• Gastroenterology
• Parasitology
• Stem Cell Biology

Background:

• Enteric helminths interact closely with the intestinal epithelium.
• The direct impact of helminths on epithelial stem cell fate remains unclear.

Purpose of the Study:

• To investigate how Heligmosomoides polygyrus bakeri (Hpb) infection affects intestinal epithelial stem cell fate.
• To elucidate the mechanisms by which Hpb manipulates the host intestinal stem cell compartment.

Main Methods:

• Infection of mice with Heligmosomoides polygyrus bakeri (Hpb).
• Organoid-based studies utilizing parasite-derived excretory-secretory products.
• Analysis of host-parasite interactions and epithelial cell differentiation.

Main Results:

• Hpb infection induces a fetal-like intestinal epithelium with Clusterin-expressing revival stem cells (revSCs).
• Hpb-driven revSC generation is independent of host immune signals.
• Parasite excretory-secretory products inhibit type 2 cytokine-driven secretory epithelial differentiation.
• Type 2 cytokines limit revSC differentiation, impacting Hpb fitness.

Conclusions:

• Helminths actively reprogram host intestinal stem cells to promote their own survival.
• A competitive interaction exists between helminths and the host for control of the intestinal stem cell niche.
• Understanding this interaction offers insights into host-parasite dynamics and potential therapeutic targets.