Upconversion optogenetic micro-nanosystem optically controls the secretion of light-responsive bacteria for systemic immunity regulation

Chun Yang,Jin Chang,Hanjie Wang,Shixing Wang,Ning Ma,Huizhuo Pan,Meihui Cui,Jing Liu,Tao Sun,Yingying Zhang

doi:10.1038/s42003-020-01287-4

Chun Yang, Jin Chang + Show 8 more

Open Access

https://doi.org/10.1038/s42003-020-01287-4

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Abstract

Chemical molecules specifically secreted into the blood and targeted tissues by intestinal microbiota can effectively affect the associated functions of the intestine especially immunity, representing a new strategy for immune-related diseases. However, proper ways of regulating the secretion metabolism of specific strains still remain to be established. In this article, an upconversion optogenetic micro-nanosystem was constructed to effectively regulate the specific secretion of engineered bacteria. The system included two major modules: (i) Modification of secretory light-responsive engineered bacteria. (ii) Optical sensing mediated by upconversion optogenetic micro-nanosystem. This system could regulate the efficient secretion of immune factors by engineered bacteria through optical manipulation. Inflammatory bowel disease and subcutaneously transplanted tumors were selected to verify the effectiveness of the system. Our results showed that the endogenous factor TGF-β1 could be controllably secreted to suppress the intestinal inflammatory response. Additionally, regulatory secretion of IFN-γ was promoted to slow the progression of B16F10 tumor.

Highlights

Chemical molecules secreted into the blood and targeted tissues by intestinal microbiota can effectively affect the associated functions of the intestine especially immunity, representing a new strategy for immune-related diseases
Ohlendorf et al.[23] constructed a single plasmid system pDawn based on the YFl/FiXJ system, which could efficiently initiate the expression of subsequent genes once absorbing blue light
To verify the light response efficiency of the pDawn plasmid system, the green fluorescent protein (GFP) gene was introduced to downstream fragments as a reporter gene

Summary

Introduction

Chemical molecules secreted into the blood and targeted tissues by intestinal microbiota can effectively affect the associated functions of the intestine especially immunity, representing a new strategy for immune-related diseases. An upconversion optogenetic micro-nanosystem was constructed to effectively regulate the specific secretion of engineered bacteria. (ii) Optical sensing mediated by upconversion optogenetic micro-nanosystem This system could regulate the efficient secretion of immune factors by engineered bacteria through optical manipulation. The core link was the construction of lightresponsive engineered bacteria plasmids using genetic manipulation techniques This plasmid was used as a genetic vector for the directional construction of optogenetic engineered strains, which can effectively secrete immunoactive molecules by optical manipulation. Compared with traditional microbiota transplantation methods (including probiotics and FMT), this regulation model had the advantages of high efficiency and sensitivity for the secretion regulation of engineered bacteria and the reduced toxic side effects. Based on the above two immune-related diseases, we will discuss the significance of the “light-responsive strain-immunity” regulatory model and the possibility of guiding the prevention and remission of related diseases (Fig. 1)

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