Uncovering How Deadly Bacteria Trick the Immune System

In the skid row area of downtown Los Angeles, an outbreak of tuberculosis may have exposed up to 4,500 individuals to the bacterium that causes the deadly disease. The outbreak has left federal officials scrambling to intervene. The outbreak is occurring during winter, when homeless individuals are driven to crowded shelters, when influenza is peaking and when people's vitamin D levels, typically boosted by sunlight exposure, are low. A new UCLA study offers critical insight into how various bacteria may manipulate such factors to their advantage.

In a study published online Feb. 28 in the journal Science, UCLA researchers demonstrate that certain cunning bacteria — including the type that causes tuberculosis — can pretend to be viruses when infecting humans, allowing them to hijack the body's immune response so that they can hide out, unhindered, inside our cells. The findings may also help explain how viral infections like the flu make us more susceptible to subsequent bacterial infections such as pneumonia.

The study is particularly relevant to tuberculosis, which kills 1.4 million people worldwide each year. In the case of the recent Los Angeles outbreak, the findings could provide clues as to how the flu and a lack of vitamin D may have given the tuberculosis bacterium an edge.

"With 8.7 million in the world falling ill with tuberculosis each year, a better understanding of how these bacteria avoid our immune system could lead to new ways to fight them and to better, more targeted treatments," said senior author Dr. Robert L. Modlin, chief of dermatology at the David Geffen School of Medicine at UCLA and a professor of microbiology, immunology and molecular genetics in the UCLA Division of Life Sciences.

The protection our immune system provides against bacteria-based diseases and infections depends on the critical response of T cells — white blood cells that play a central role in fighting infections — and in particular on the release of a protein called interferon-gamma. Interferon-gamma utilizes the vitamin D hormone to alert and activate cells to destroy invading bacteria.

The research team found that bacteria can pretend to be viruses, triggering the immune system to launch an attack with a different protein, called interferon-beta, which is designed to fight viruses, not bacteria. Not only is interferon-beta ineffective against bacteria, but it can also block the action of interferon-gamma, to the advantage of bacteria. Further, if a real virus were to infect the body, triggering interferon-beta, it would divert the attention of the immune response, preventing an attack on the bacterial invader. The researchers say this may explain why the flu can lead to a more serious bacterial-based infection like pneumonia. "Like a wolf in sheep's clothing, the bacteria can fool the immune system into launching an attack against the wrong type of infection, thus weakening the response against the bacteria," said first author Rosane M. B. Teles, a researcher in the dermatology division at the Geffen School of Medicine.

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For the study, the team examined the mechanisms by which the virus-fighting interferon-beta protein suppresses the interferon-gamma defense response to bacterial infections, tricking the immune system into making the wrong defense choices.

Source-Eurekalert