Interaction between tissue-dwelling helminth and the gut microbiota drives mucosal immunoregulation

Area of Science:

• Immunology
• Microbiology
• Parasitology

Background:

• Tissue-dwelling helminths modulate host immunity, often promoting regulatory T cells (Tregs) and altering the gut microbiome.
• The specific role of the gut microbiota in the immunomodulatory effects of non-intestinal parasites remains largely unknown.

Purpose of the Study:

• To investigate the tripartite relationship between host, extraintestinal helminth (larval Echinococcus multilocularis), and gut bacteria in regulating colonic Tregs.
• To elucidate the mechanisms by which gut microbiota contribute to the anti-inflammatory responses induced by helminth infection.

Main Methods:

• Utilized a murine model of larval Echinococcus multilocularis infection.
• Employed fecal microbiota depletion and transplantation to assess the role of gut bacteria.
• Conducted shotgun metagenomic and metabolic analyses of the gut microbiome.
• Investigated the effect of specific bacterial strains, like Lactobacillus reuteri, on Treg populations.

Main Results:

• Larval E. multilocilocularis infection attenuated colitis and increased colonic Foxp3+ Treg populations in mice.
• Gut microbiota were essential for the helminth-induced Treg expansion.
• Infection led to significant shifts in gut microbiome structure, notably an increase in Lactobacillus reuteri.
• Microbial metabolism was reprogrammed to produce more short-chain fatty acids, known Treg regulators.
• Elevated L. reuteri levels were sufficient to promote colonic Treg frequency.

Conclusions:

• Extraintestinal helminth infection drives the expansion of host colonic Tregs via modulation of the gut microbiome.
• The gut microbiome acts as a critical mediator of anti-inflammatory effects, even in therapies involving extraintestinal helminths.
• This highlights the gut microbiome's importance in the host-parasite interaction and potential therapeutic strategies.