A metabolically engineered bacterium controls autoimmunity and inflammation by remodeling the pro-inflammatory...

Area of Science:

• Immunology
• Microbiology
• Metabolic Engineering

Background:

• Immunotherapy shows promise for autoimmune disorders but is limited by the pro-inflammatory microenvironment.
• Developing novel immunomodulatory agents is crucial for enhancing current therapeutic strategies.

Purpose of the Study:

• To metabolically engineer a bacterial strain to produce indole, a regulator of regulatory T cell function.
• To evaluate the therapeutic potential of this engineered bacterium in autoimmune disease models.

Main Methods:

• Metabolic engineering of *Brucella melitensis* 16M ∆vjbR to express tnaA, creating Bm∆vjbR::tnaA for indole production.
• Assessing the impact of Bm∆vjbR::tnaA on macrophage polarization and regulatory T cell function.
• Evaluating the efficacy of Bm∆vjbR::tnaA, alone and in combination with adoptive T cell transfer, in a murine model of autoimmune arthritis.

Main Results:

• Treatment with Bm∆vjbR::tnaA induced anti-inflammatory macrophages producing IL-10.
• The engineered bacteria promoted regulatory T cell function.
• Combined treatment with Bm∆vjbR::tnaA and regulatory T cell adoptive cell transfer significantly reduced autoimmune arthritis incidence, severity, and joint damage.

Conclusions:

• Metabolically engineered bacteria can serve as effective vehicles for immunotherapy delivery.
• This strategy remodels the pro-inflammatory microenvironment and enhances regulatory T cell function to combat autoimmunity.
• Indole-producing engineered bacteria offer a promising approach to improve immunotherapy efficacy for autoimmune and pro-inflammatory disorders.