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Tuberculosis bacterium's outer cell wall disarms the body's defense to remain infectious
Date:10/3/2011

lent TB bacterium produced significantly less TNF than lipomannan from the M. smegmatis bacterium.

Though the study showed that the harmless cells increase production of TNF through a well-known receptor pathway as expected, the virulent TB bacteria did not make use of that receptor pathway. This supported the concept that the pathogenic TB bacterium has figured out another way to block the TNF protein in its quest to keep the immune system guessing, said Schlesinger, also the director of Ohio State's Center for Microbial Interface Biology.

A single microRNA can affect the production of hundreds of proteins, and the process of identifying those relationships is ongoing. However, two microRNAs in this study were known to be relevant for their connections to genes and proteins already established as players in the immune response to TB infection: miR-125b and miR-155.

Biochemical and genetic experiments showed that macrophages stimulated with lipomannan from TB bacteria had enhanced expression of miR-125b, effectively inhibiting the production of TNF. In contrast, the lipomannan from the harmless bacteria had enhanced expression of miR-155, which regulates other compounds in a way that stimulates TNF production.

Researchers' experimental manipulation to lower the expression of miR-125b in macrophages increased production of TNF in response to the TB bacteria lipomannan, further confirming that this regulation of TNF occurred at the microRNA level, Schlesinger said.

"This really speaks to the power of the tuberculosis bacterium to adapt to the human host," he said. "It has had centuries to develop a sophisticated way to deal with its encounter with the human. Fortunately, genomic technology is allowing us to identify microRNAs more and more rapidly, which might allow us to catch up with the TB bacterium and figure out a way to outsmart it."


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Contact: Larry Schlesinger
larry.schlesinger@osumc.edu
614-292-8789
Ohio State University
Source:Eurekalert

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