Young mice expel the tapeworm Hymenolepis diminuta and are protected from colitis by triggering a memory response with worm antigen

Abstract

Infection with helminth parasites reduces the severity of concomitant inflammatory disease in adult mice. There is an alarming increase of inflammatory bowel disease (IBD) in children. It is important to determine whether helminth therapy would be of value in pediatric IBD and whether triggering immunological memory to the worm would be anticolitic. Three-week-old (young) and eight-week-old (adult) Balb/c mice were infected with H. diminuta, and infectivity and T helper 2 (Th2) immunity were assessed. Other mice received H. diminuta with or without a crude worm extract ( HdE) 28-42 days postinfection (dpi) with or without dinitrobenzene sulphonic acid [DNBS, 1.5 mg (young) or 3 mg (adults), ir], and colitis was assessed 72 h later. Infected young mice developed Th2 immunity and expelled H. diminuta; expulsion was delayed by ~2 days compared with adult mice. Colitis, as gauged by macroscopic disease and histopathology scores, was less severe in young mice infected 10 days, but not 8 days, before DNBS. Protection against DNBS-induced colitis was accompanied by an increased capacity to make interleukin (IL)-4 and IL-10. Mice infected with H. diminuta were not protected from DNBS-colitis when challenged 28 days later; however, injection of these mice with HdE coincident with DNBS resulted in less disease and increased splenic IL-4 and IL-10. Using a boost (500 μg HdE, 28 dpi) and repeat HdE (100 μg, 42 dpi) regimen with infected mice suppressed DNBS-colitis, as did adoptive transfer of splenic CD4 T cells from infected mice with low-dose HdE challenge. Should these data translate to IBD, then helminth therapy could be of value in pediatric-onset IBD, and defining the antigen(s) that elicit antihelminth immunological memory could serve as an anticolitic approach in previously infected individuals. NEW & NOTEWORTHY This study demonstrates that juvenile mice are protected from colitis by infection with the tapeworm Hymenolepis diminuta and that using worm antigen to trigger an immunological memory response in previously infected mice can be used to limit the severity of colitis.

Nrf2 Participates in M2 Polarization by Trichinella spiralis to Alleviate TNBS-Induced Colitis in Mice

“…Crohn’s disease (CD) is a chronic dysregulated inflammatory disease of intestinal tract. Several studies have demonstrated the therapeutic potential of helminths in the treatment of colitis ( 25 – 27 ). Previously, we have demonstrated that infection of Trichinella spiralis reduce the severity of TNBS –induced colitis ( 28 ).…”

Selected Molecular Mechanisms Involved in the Parasite–Host System Hymenolepis diminuta–Rattus norvegicus

“…Reyes (2015) showed that CD19+ lymphocytes from H. diminuta –infected mice reduced the effects of DNBS, and thus promoted the suppression of colitis [ 115 ]. In turn, Arai et al (2018) showed that the H. diminuta antigen inducing an immune response in previously infected mice could be used to limit the severity of colitis regardless of the age of the host [ 118 ]. Graepel (2013) [ 111 ] found an exacerbation of the disease as a result of H. diminuta infection in a mouse with rheumatoid arthritis.…”

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

“…Three-week-old mice infected with H. diminuta were also protected from DNBS-induced colitis; however, the kinetics of this response differed from adult mice: young mice displayed less colitis when infected 10 days, but not 8 days, prior to treatment with DNBS [ 10 ]. This delay in the anti-colitic effect could be due to immaturity of the immune system in the young mouse, and it draws attention to the importance of the kinetics of the infection-colitis regimen.…”

“…Studies with H. diminuta in the dextran sodium sulphate (DSS) [ 9 ] and di-nitrobenzene sulphonic acid (DNBS) [ 3 ] murine models of colitis were among the first to provide proof-of-concept data in support of helminth therapy to reduce the severity of colonic inflammation and concomitant signs of disease. While ongoing studies have confirmed the anti-colitic effect in the DNBS-model and revealed some of the nuances of the helminth–host interaction [ 10 , 11 , 12 ], two major questions remain unaddressed: both germane to helminth therapy: First, what is the temporal window of opportunity for H. diminuta to suppress colitis? Elucidation of the kinetics of infection in the context of inflammation can provide insight into host–parasite interaction and potentially reveal new targets for therapeutic intervention.…”