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

COLUMBUS, Ohio -- The bacterium that causes tuberculosis has a unique molecule on its outer cell surface that blocks a key part of the body's defense. New research suggests this represents a novel mechanism in the microbe's evolving efforts to remain hidden from the human immune system.

Researchers found that the TB bacterium has a molecule on its outer surface called lipomannan that can stop production of an important protein in the body's immune cells that helps contain TB infection and maintain it in a latent state. This protein is called tumor necrosis factor (TNF). When TNF is not produced in sufficient quantities, the TB bacterium can grow unchecked and cause an uncontrolled active infection inside and outside of the lungs.

"There are several unique components on the Mycobacterium tuberculosis outer cell wall that help it sneak into the lung relatively unnoticed," said Larry Schlesinger, professor and chair of the Department of Microbial Infection and Immunity at Ohio State University and senior author of the study. "The more we can learn about how these cell wall structures influence the human immune response, the closer we can get to developing a more effective strategy to treat or even prevent an active tuberculosis infection."

Lipomannan resembles a tree branch sprinkled with smaller sugar molecules protruding from the outer cell wall of the bacterium. The findings show that lipomannan can block TNF production at the microRNA level. MicroRNAs are small segments of RNA that regulate -- or fine-tune -- a gene's protein-building function.

To date, microRNAs have been implicated most frequently in the development of cancer. Schlesinger said this research is among the first studies to show that pathogenic bacteria can influence microRNA activation in immune cells and is the first to explore how microRNAs regulate the macrophage inflammatory response to Mycobacterium tuberculosis.

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

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