Work

Engineering microbes to modulate innate immune signaling: strategies for host–microbe interactions

Year: 2025

Type: review

Abstract: The human gastrointestinal tract hosts a dense microbial community that closely interfaces with the mucosal immune system to preserve homeostasis. While dysregulation of this interaction contributes to certain disease states, through targeted microbial engineering, these interactions can be modulated for therapeutic benefit. Although engineered microbial therapeutics have shown encouraging preclinical results, few approaches have progressed into clinical pipelines. This gap highlights the need for engineered microbes with greater precision, reliability, and context-dependent control. The innate immune system is primed to rapidly sense microbial signals through pattern recognition receptors and provides accessible and tractable targets for such interventions. This review highlights four strategies that have used engineered probiotics to modulate innate immunity: (1) direct immune cell engagement through surface-display, (2) production of soluble immune effectors, (3) extracellular vesicles for delivery of immune modulators, and (4) environmentally responsive systems to enable spatial and temporal control over immune modulation. Bridging microbial engineering with mucosal immunology can enable engineered probiotics to function as dynamic, context-aware immunomodulators. • Engineered microbes can precisely modulate innate immune pathways in the gut. • Surface display enables direct engagement of host pattern recognition receptors. • Microbes secrete immune effectors to locally regulate innate inflammatory signals. • Microbial vesicles offer stable, targeted delivery of innate immune modulators. • Biosensing circuits enable context-dependent and self-regulated immune control.

Source: Current Opinion in Microbiology

DOI: 10.1016/j.mib.2025.102695

Authors: Shanna Bonanno, Neel S Joshi

Institution: Northeastern University

Language: English

Topic: Probiotics and Fermented Foods

Subfield: Food Science

Field: Agricultural and Biological Sciences

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,800