Chemical probe helps understand immune response

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A trio of chemists from Indiana University Bloomington have created a new sensor to detect chemical changes in immune cells as pathogens break down. The work could potentially contribute to the early diagnosis and treatment of infectious diseases, such as tuberculosis, which elude certain elements of the body’s immune response.

The results were published on October 8 in Angewandte Chemie, a leading chemistry journal. The study was led by Yan Yu, associate professor in the chemistry department at IU Bloomington College of Arts and Sciences.

The particles in the study were designed to understand phagocytosis, the process by which immune cells absorb and destroy pathogens in the body. During this important process, pathogens are engulfed in cell compartments called phagosomes, which then “mature” through a complex sequence of chemical reactions, killing invading diseases.

“Many important cellular functions, including phagocytosis, rely on the orchestration of complex chemical reactions, but measuring these different reactions in real time inside a living cell is extremely difficult,” Yu said. study shows that particles of the type designed in our laboratory are widely applicable to understanding many types of complex chemical interactions in living cells. “

The particles used in the study are called Janus particles, named after the two-sided Roman god. Artificially constructed particles are so named because both sides of the same particle are “coated” with different chemical sensors. These sensors can serve as detectors or “reporters” for various chemicals involved in the biological process under study.

Yu’s lab developed a technique to cluster these receptors very close to each other on the surface of a Janus particle, greatly increasing their effectiveness as an investigative tool.

Yu’s previous research on Janus particles has yielded new insight into the body’s ability to resist fungal infections, as well as a new method for activating the body’s T cells, which are used to fight cancer, improve health. immune therapy, fight viral infections and induce tolerance. in autoimmune diseases. This latter work is the subject of a patent filing with the US Patent and Trademark Office. She also filed a provisional patent on the newly reported discovery.

In the new study, Yu’s team designed a Janus particle whose two sides consist of a 3 micron pH reporter and a 500 nanometer proteolysis reporter. As a result, the researchers were able to simultaneously measure two chemical processes involved in phagocytosis – acidification and proteolysis – within a single maturing phagosome in real time. They identified that phagosomes need “acidic light” to activate enzymes that digest pathogens encapsulated within, a critical step in preventing pathogens from reproducing inside immune cells of the cell. ‘host.

They also showed that lipopolysaccharide, a sugar compound found in the membranes of the outer wall of many bacteria, can affect the acidification and proteolysis of phagosomes.

Understanding these processes is particularly important in bacterial infections which evade the body’s immune response by diverting one or more events from the phagosome maturation process, thereby thwarting the protective function of the phagosome. These diseases include tuberculosis, which is the world’s leading fatal infectious disease, killing an estimated 1.5 million each year.

“The Janus particles created in this study act as a sensor to detect these chemical changes inside immune cells as pathogens break down,” Yu said. “But, more broadly, the work highlights feasibility Janus particles as a general tool to monitor multiple reactions within a cell – and demonstrate their potential for the detection and diagnosis of infectious diseases. “

Reference
Lee S, Zhang Z, Yu Y. Simultaneous real-time imaging of acidification and proteolysis in single phagosomes using bifunctional Janus particle probes. Ang Chem, online October 8, 2021. doi: 10.1002 / anie.202111094

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