Cell-analysis technique could combat tuberculosis
Medikoe Health Expert
Koramangala, bengaluru, karnataka, india, Bengaluru Jul 29, 2021
A new method that investigates how individual immune cells react to the bacteria causing tuberculosis could pave the way for new vaccine approaches against this deadly disease and give insights into combating other infectious diseases worldwide.
Rise of Cell-Analysis Technique for Tuberculosis
- The cutting-edge technologies were developed in the laboratory of Dr David Russell, the William Kaplan Professor of Infection Biology in the Department of Microbiology and Immunology in the College of Veterinary Medicine, and reported in new research published in the Journal of Experimental Medicine on July 22.
- For years, Russell's laboratory has attempted to unravel how Mycobacterium tuberculosis (Mtb), bacteria causing tuberculosis, infect and persist in their host cells, which are typically immune cells called macrophages.
- The laboratory's latest innovation merges two analytical tools that each target a distinct side of the pathogen-host relationship: "reporter" Mtb bacteria that radiate different colours depending on how stressed they are in their environment; and single-cell RNA sequencing (scRNA-seq), which admits RNA transcripts of individual host macrophage cells.
- For the first time ever, these two approaches are combined to analyze Mtb-infected immune cells from an in vivo infection.
- After contaminating mice with the fluorescent reporter Mtb bacteria, Russell's team was capable of gathering and flow-sorting individual Mtb-infected macrophages from the mouse lung.
- The researchers then concluded which macrophages promoted Mtb growth (sporting happy, red-glowing bacteria) or carried stressed Mtb unlikely to grow (unhappy, green-glowing bacteria).
- Next, they used the two sorted, infected macrophage populations and moved them through single-cell RNA sequencing analysis, thereby creating transcriptional profiles of each individual host cell in both populations.
- When the researchers compared the macrophage single-cell sequencing data with the reporter bacteria phenotype, they discovered an almost perfect one-to-one relationship between the transcriptional profile in the host cell and the fitness status of the bacterium.
- The finding sets a foundation for more powerful studies on how pathogens attack individual cells and could be used in the research of any intracellular pathogen, including viruses, and is easily applicable to any animal challenge model.
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