Related Experiment Video
Updated: Feb 25, 2026
Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice
Published on: December 16, 2021
The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon
A R Krarup1, M Abdel-Mohsen2,3,4, M H Schleimann1
1Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Abstract:
Toll-like receptor 9 (TLR9) agonists are being developed for treatment of colorectal and other cancers, yet the impact of these drugs on human intestines remains unknown. This, together with the fact that there are additional potential indications for TLR9 agonist therapy (e.g., autoimmune and infectious diseases), led us to investigate the impact of MGN1703 (Lefitolimod) on intestinal homeostasis and viral persistence in HIV-positive individuals. Colonic sigmoid biopsies were collected (baseline and week four) from 11 HIV+ individuals on suppressive antiretroviral therapy, who received MGN1703 (60 mg s.c.) twice weekly for 4 weeks in a single-arm, phase 1b/2a study. Within sigmoid mucosa, global transcriptomic analyses revealed 248 modulated genes (false discovery rate<0.05) including many type I interferon (IFN)-stimulated genes. MGN1703 increased the frequencies of cells exhibiting MX1 (P=0.001) and ISG15 (P=0.014) protein expression. No changes were observed in neutrophil infiltration (myeloperoxidase; P=0.97). No systematic effect on fecal microbiota structure was observed (analysis of similarity Global R=-0.105; P=0.929). TLR9 expression at baseline was inversely proportional to the change in integrated HIV DNA during MGN1703 treatment (P=0.020). In conclusion, MGN1703 induced a potent type I IFN response, without a concomitant general inflammatory response, in the intestines.
Insights
The Toll-like receptor 9 (TLR9) agonist MGN1703 induced a strong type I interferon response in the intestines of HIV-positive individuals. This treatment did not cause general inflammation or alter gut microbiota, showing potential for immune modulation.
Area of Science:
- Immunology
- Gastroenterology
- Virology
Background:
- Toll-like receptor 9 (TLR9) agonists are investigated for cancer therapy.
- The intestinal effects of TLR9 agonists, including MGN1703 (Lefitolimod), are not well understood.
- Potential applications include autoimmune and infectious diseases, necessitating intestinal impact studies.
Purpose of the Study:
- To investigate the impact of MGN1703 on intestinal homeostasis and viral persistence in HIV-positive individuals.
- To assess the immunomodulatory effects of MGN1703 in the colonic mucosa.
Main Methods:
- Colonic sigmoid biopsies were collected from 11 HIV+ individuals before and after 4 weeks of MGN1703 treatment.
- Global transcriptomic analysis identified modulated genes, including type I interferon-stimulated genes.
- Protein expression of MX1 and ISG15, neutrophil infiltration, and fecal microbiota structure were analyzed.
Main Results:
- MGN1703 treatment led to significant modulation of 248 genes, predominantly type I interferon-stimulated genes.
- Increased frequencies of cells expressing MX1 and ISG15 proteins were observed.
- No significant changes in neutrophil infiltration or fecal microbiota structure were detected.
- Baseline TLR9 expression inversely correlated with changes in integrated HIV DNA.
Conclusions:
- MGN1703 induces a potent type I interferon response within the intestinal mucosa.
- The treatment did not elicit a general inflammatory response in the intestines.
- MGN1703 may influence viral persistence, warranting further investigation.
More Related Videos
08:37Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
10:10Experimental Infection with Listeria monocytogenes as a Model for Studying Host Interferon-γ Responses
Published on: November 16, 2016
