Enhancing macrophages to combat intracellular bacteria

Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China *Correspondence: hy.wang1@siat.ac.cn (H.W.); paul.chu@cityu.edu.hk (P.C.) Received: August 14, 2023; Accepted: September 6, 2023; Published Online: September 7, 2023; https://doi.org/10.59717/j.xinn-life.2023.100027 © 2023 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Citation: Wu Y., Wang H., and Chu P. (2023). Enhancing macrophages to combat intracellular bacteria. The Innovation Life 1(2), 100027. People have taken the initiative to combat pathogenic bacteria for more than 100 years since some microbes have been found to cause diseases. The struggle between human beings and pathogens can be regarded as an arms race, in which antibacterial materials become smarter to kill bacteria, while bacteria in turn evolve to be stronger to increase survival. Antibiotic therapies, as the primary clinical treatment for bacterial infections, seem trapped in a vicious cycle because the corresponding drug-resistant bacteria emerge rapidly within a few years after the clinical application of a new antibiotic. To get out of this vicious cycle, scientists have to explore new strategies to counter bacterial threats through antibiotic-free treatments or improving antibiotic utilization, in which methods to eliminate pathogens by mobilizing immune cells draw considerable attention. Macrophages, the representative immune cells, are able to remove pathogens in vivo by identification, endocytosis, sterilization, and digestion. Briefly, the Toll-like receptors (TLRs) on the macrophage membrane can recognize the pathogen-associated molecular patterns (PAMPs), resulting in the response to pathogens and inducing endocytosis thereafter. During endocytosis, the cell membrane protrudes and fuses to form a phagosome, which encloses the pathogens. In the phagosome, pathogens are inactivated by the synergistic effects of reactive oxygen species (ROS), reactive nitrogen species (RNS), free fatty acids, etc., and degraded by the hydrolases from the lysosomes fusing with the phagosome. Now that the innate macrophage can help eliminate the bacteria in vivo, why is there a need to develop new antibacterial strategies? That is because many bacteria have evolved to