Infection with Hymenolepis diminuta Blocks Colitis and Hastens Recovery While Colitis Has Minimal Impact on Expulsion of the Cestode from the Mouse Host.

Shuhua Li,Arthur Wang,Derek M Mckay,Sruthi Rajeev

doi:10.3390/pathogens10080994

Abstract

Two experimental paradigms were adopted to explore host–helminth interactions involved in the regulation of colitis and to understand if colitis affects the outcome of helminth infection. First, male BALB/c mice infected with H. diminuta were challenged 4 days later with dinitrobenzene sulphonic acid (DNBS) and necropsied 3 days later. Second, mice were infected with H. diminuta 3 days after DNBS treatment and necropsied 11 or 14 days post-DNBS. Mice were assessed for colitic disease severity and infectivity with H. diminuta upon necropsy. Supporting the concept of helminth therapy, mice are protected from DNBS–colitis when infected with H. diminuta only 4 days previously, along with parallel increases in splenic production of Th2 cytokines. In the treatment regimen, H. diminuta infection produced a subtle, statistically significant, enhanced recovery from DNBS. Mice regained body weight quicker, had normalized colon lengths, and showed no overt signs of disease, in comparison to the DNBS-only mice, some of which displayed signs of mild disease at 14 days post-DNBS. Unexpectedly, colitis did not affect the hosts’ anti-worm response. The impact of inflammatory disease on helminth infection is deserving of study in a variety of models as auto-inflammatory diseases emerge in world regions where parasitic helminths are endemic.

Highlights

Accepted: 2 August 2021The increased prevalence of auto-inflammatory conditions, such as diabetes, arthritis, multiple sclerosis, and inflammatory bowel disease (IBD), coupled with a lack of cures for these conditions underscores the need for innovative approaches to manage idiopathic disease [1]
Numerous studies with helminth–rodent model systems have shown that deliberate infection with parasitic helminths can reduce inflammation [20,21,22]
The consensus on the mechanism of helminth therapy is essentially two-fold: Infection with parasitic helminths drives Th2-dominated immunity and this reduces disease caused by Th1 immunopathology, or mobilization of immunoregulatory cells/factors inhibits inflammation (e.g., Foxp3+ regulatory T cells (Tregs), alternatively activated macrophages (AAMs), IL-10, transforming growth factor β (TGFβ)) [21,26]

Summary

Introduction

Accepted: 2 August 2021The increased prevalence of auto-inflammatory conditions, such as diabetes, arthritis, multiple sclerosis, and inflammatory bowel disease (IBD), coupled with a lack of cures for these conditions underscores the need for innovative approaches to manage idiopathic disease [1]. Use of animal models of disease, especially colitis, has repeatedly shown that infection with a variety of parasitic helminths can reduce the severity of inflammatory disease [3,4,5,6,7]. Bearing no teeth or hooks, it does no obvious abrasive damage to the host. It is not auto-infective and its life-cycle requires an invertebrate host, so there is no direct person-to-person spread. Studies with H. diminuta in the dextran sodium sulphate (DSS) [9] and di-nitrobenzene sulphonic acid (DNBS) [3] murine models of colitis were

Methods

Results

Conclusion