Decoration of Biomimetic DNA Receptors on Macrophages for Precise and Logical Manipulation of Pathogen Predation

Macrophages use pattern recognition receptors (PRRs) to recognize, capture, and phagocytize pathogens. Recreating artificial systems to mimic such receptors for manipulating macrophage predation is both scientifically exciting and technologically relevant to anti-infection. Nevertheless, fabricating synthetic PRR-mimicking receptors with a predictable and stable structure remains a challenge. Herein, we use circular aptamers as building blocks to create artificial DNA receptors (ADRs) that mimic the function of PRRs. After modification of ADRs on macrophages, they can stably recognize specific pathogens and promote the phagocytosis of macrophages, akin to natural PRRs. As dynamic structures, these ADRs can be flexibly activated or inactivated by external DNA molecules, akin to protein receptors responding to small-molecule ligands. Owing to the programmability of the DNA reaction, Boolean logic operations can be introduced to logically manipulate the predation behavior of macrophages, exhibiting the characteristics of artificial receptors. Furthermore, ADRs can be integrated with other functional DNA motifs, e.g., CpG DNA, to enhance the activation and antibacterial capacity of macrophages with higher efficiency. Overall, we believe that this artificial receptor not only broadens the application of DNA nanotechnology in cell biology but also contributes to ongoing efforts to remodel the innate immune system for fighting infection in consideration of the growing emergence of multidrug-resistant bacteria.