A metabolically engineered bacterium controls autoimmunity and inflammation by remodeling the pro-inflammatory microenvironment
| Autor: | Jugal Kishore Das, Fengguang Guo, Carrie Hunt, Shelby Steinmeyer, Julia A Plocica, Koichi S. Kobayashi, Yufang Ding, Arul Jayaraman, Thomas A Ficht, Robert C. Alaniz, Paul de Figueiredo, Jianxun Song |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Gut Microbes, Vol 14, Iss 1 (2022) |
| Druh dokumentu: | article |
| ISSN: | 19490976 1949-0984 1949-0976 |
| DOI: | 10.1080/19490976.2022.2143222 |
| Popis: | Immunotherapy has led to impressive advances in the treatment of autoimmune and pro-inflammatory disorders; yet, its clinical outcomes remain limited by a variety of factors including the pro-inflammatory microenvironment (IME). Discovering effective immunomodulatory agents, and the mechanisms by which they control disease, will lead to innovative strategies for enhancing the effectiveness of current immunotherapeutic approaches. We have metabolically engineered an attenuated bacterial strain (i.e., Brucella melitensis 16M ∆vjbR, Bm∆vjbR::tnaA) to produce indole, a tryptophan metabolite that controls the fate and function of regulatory T (Treg) cells. We demonstrated that treatment with Bm∆vjbR::tnaA polarized macrophages (Mφ) which produced anti-inflammatory cytokines (e.g., IL-10) and promoted Treg function; moreover, when combined with adoptive cell transfer (ACT) of Treg cells, a single treatment with our engineered bacterial strain dramatically reduced the incidence and score of autoimmune arthritis and decreased joint damage. These findings show how a metabolically engineered bacterium can constitute a powerful vehicle for improving the efficacy of immunotherapy, defeating autoimmunity, and reducing inflammation by remodeling the IME and augmenting Treg cell function. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
|