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Researchers find new way tuberculosis suppresses immunity

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According to the WHO, tuberculosis sickens about 10 million people and kills 1-2 million people each year. This new discovery may point to an effective target for a gene-based treatment or preventative therapy.

Multidrug-resistant tuberculosis poses a public health threat in many parts of the world, despite the fact that available treatments are only 85 percent effective.

The study was published in the journal PLOS Pathogens on July 29, 2021.

Volker Briken and his team made their discovery by infecting a type of white blood cell called a macrophage with either Mtb — the bacterium that causes tuberculosis — or a non-virulent bacterium and observing the cell’s response.

The inflammasome, a complex of proteins, was dramatically reduced in Mtb-infected cells but not in non-virulent bacteria-infected cells, according to the researchers. The inflammasome searches the interior of a cell for pathogens before signalling the cell to initiate an immune response.

“It was very unexpected for us to find this primary observation that Mtb can actually inhibit the inflammasome,” Briken said.

“The infection also causes some minor activation of the inflammasome, and so no one bothered to look for a potential of Mtb to inhibit the process. It is a classic example of the tug of war between the pathogen wanting to suppress host immunity and the host cell sensing the pathogen to activate immune responses.”

The team then wanted to know if the inflammasome was suppressed by a specific Mtb gene. The researchers used Mtb mutants to infect new macrophages after inserting Mtb genes into a non-virulent mycobacterium species.

They found that infections with non-virulent bacteria carrying the Mtb gene PknF inhibited the host cell’s inflammasome response.

“We don’t know how this gene inhibits the inflammasome,” Briken said, “but the function of this gene is to regulate the production and/or secretions of lipids, so we think maybe the bacterium modifies lipid secretion in a way that influences the inflammasome. That is what we will be investigating in future studies.”

Briken is interested in determining how PknF suppresses the host cell’s inflammasome. He and his colleagues are also investigating the role of PknF in the disease’s virulence.

If it is discovered that inhibiting the inflammasome enhances the virulence of Mtb, the PknF gene may become a good target for future drug therapies to treat the disease.

Image Credit: Getty

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