Manipulating The 'Switching Time' In Immune Response Could Help To Fight Tuberculosis

Researchers at Ohio State University say that fighting tuberculosis or other airborne pathogens could only be a matter of manipulating what is called the "switching time" in immune response.

They define 'switching time' as the point at which a highly regulated immune response gives way to powerful cells that specialize in fighting a specific invading bug.

For dealing with tuberculosis, the researchers are using mathematical modeling to determine whether a change to the natural switching time would result in a more effective immune response.

They are also analyzing which parts of the immune response are most important to striking a balance between properly timing the switch and killing the microbe.

The complex modeling considers the huge assortment of cells and molecules at work in the human immune response to Mycobacterium tuberculosis, the microbe that causes TB.

The modeling suggests that the average switching time occurs about 50 days after tuberculosis invades the lung, which roughly coincides with clinical expectations that a skin test will turn up positive for TB between four and eight weeks after infection.

But, by that time, bacteria have settled in and are harder to kill, even with the more robust immune response.

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The launch of the stronger immune response goes unnoticed in about 90 percent of infections Because TB is highly evolved and adapted to the human host.

With less adapted but virulent pathogens, on the other hand, an individual becomes acutely ill, and sometimes dies, when the switching time occurs.

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Scientists say that the mathematical models that predict relationships and interactions in the immune response could guide planning for therapies that would be designed to either accelerate or slow the switching time, depending on the pathogen.

"A great problem in developing drugs and vaccines against airborne pathogens is this apparent bottleneck in the immune response and the inability to quickly and effectively eradicate microbes in the lung environment. Understanding that bottleneck is an important part of this paper, and brings new insight into how to override the problem with tuberculosis and other pathogens," said Larry Schlesinger, a senior author of the study.

In this research, the scientists sought to determine what it would take to shorten the switching time and reduce the number of bacteria in the lung.

"If we could shorten the treatment for TB, that would be very powerful in breaking the transmission cycle," said Schlesinger.

The researchers could use the precision of the modeling to simulate outcomes resulting from multiple tweaks to the values assigned to the various immune response activities.

The research is scheduled to appear in the online early edition of the Proceedings of the National Academy of Sciences.

Source-ANI
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