News Release 

TB study reveals potential targets to treat and control infection

This is the first study to use in depth, single-cell RNA sequencing (scRNAseq) to analyze responses to TB in macaques

Texas Biomedical Research Institute

Research News

San Antonio, Texas (February 15, 2020) - Researchers at the Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute (Texas Biomed) may have found a new pathway to treat and control tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb). Using single-cell RNA sequencing (scRNAseq), a next-generation sequencing technology, scientists were able to further define the mechanisms that lead to TB infection and latency. Co-led by Deepak Kaushal, Ph.D., Director of the SNPRC, this is the first study that used scRNAseq to study TB in macaques in depth. Results from the study were published in Cell Host & Microbe.

"Single-cell RNAseq is a novel approach that has developed in the past three or four years. It's an approach that allows us to look at the immune response more granularly, in higher resolution," Dr. Kaushal explained. "We were able to identify an immune response to Mtb infection in single lung cells as the infection progressed to disease, in some cases, or was controlled in others."

The number of TB related deaths has decreased by 30% globally. However, according to the World Health Organization, 1.4 million people died from TB in 2019; the disease continues to be one of the top communicable diseases plaguing low-income countries. It's one of several diseases negatively impacted by COVID-19 due to the virus's impact on health systems worldwide. TB is primarily spread by a cough or sneeze from someone who is infected with the disease; however, people with latent TB are not contagious. The disease is both preventable and treatable, but latent TB can become active if disrupted by another invading infection, such as Human Immunodeficiency Virus (HIV) and drug resistance continues to be a major impediment.

The study highlighted that plasmacytoid dendritic cells, which sense infection in the body, overproduce Type I interferons. Plasmacytoid dendritic cells are immune cells sent out to stop a bacteria or virus from replicating or causing disease. However, an overproduction of interferons can also cause harm. In this study, scientists observed that the interferon response correlated with disease instead of control. This information is important to scientists developing TB therapeutics and vaccines. Modifications to therapeutic/vaccine formulas may be needed to address interferon signaling.

"When we have a more precise understanding of how an infection develops, that knowledge can lead us to identify new drugs or therapies to treat disease and improve vaccines," Dr. Kaushal said. "Although our findings decreased the gap in knowledge of TB disease and latent infection, there's still more we need to learn."

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This investigation used resources supported by SNPRC's grants P51 OD011133 and U42 OD010442 from the Office of Research Infrastructure Programs, National Institutes of Health. This study was performed in collaboration with Drs. Shabaana Khader and Max Artyomov at Washington University in St. Louis, as well as Dr. Smriti Mehra at Tulane University and their laboratories.

Texas Biomed is one of the world's leading independent biomedical research institutions dedicated to eradicating infection and advancing health worldwide through innovative biomedical research. Texas Biomed partners with researchers and institutions around the world to develop therapeutics and vaccines against viral pathogens causing AIDS, hepatitis, hemorrhagic fever, tuberculosis and parasitic diseases responsible for malaria and schistosomiasis disease. The Institute has programs in host-pathogen interaction, disease intervention and prevention and population health to understand the links between infectious diseases and other diseases such as aging, cardiovascular disease, diabetes and obesity. For more information on Texas Biomed, go to http://www.TxBiomed.org.

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