"The current study suggests the manner in which the TB pathogens manipulate recruitment of the first responding macrophages to gain access to their preferred niche," the researchers noted.
"The choreographed entry involves two related TB cell lipids acting in concert to avoid one host pathway while inducing another," they wrote. The findings link the previously known, absolutely essential virulence factor on the surface of TB cells, PDIM, to the evasion of immune cell detection. They also might explain why a certain pathogen molecular pattern recognition system is dispensable in protecting against TB. On the other hand, PGL is not required on the surface of TB cells for them to infect the body.
Ramakrishnan noted that globally, a lot of samples of TB taken from infected patients do not have PGL. "However," she and her research team noted, "the importance of PGL in mediating TB virulence or transmission is underscored by its presence in many of the W-Beijing strains" of TB which are starting to rapidly appear in more patient samples, and which have predominated in outbreaks in North America.
Ramakrishnan explains that their findings suggest how PGL may play an important role in increasing TB's infectivity.
"The presence of PGL in ancestral strains of TB suggest it played an integral role in the evolution of TB infectivity," the researchers noted. "TB is an ancient disease and the enhanced infectivity conferred by PGL may have been essential for most of its history before human crowding, with its increased opportunity for transmission, made it dispensable."
The study findings, and previous work on TB, might also explain why smaller droplets of TB are more infectious than larger ones. Only the smaller droplets can make their way down into the lower airways. On the flip side, all it takes is 3 or fewer TB mycobacteria with PGL-producing ability to enter the lower lung
|Contact: Leila Gray|
University of Washington