“Big-eater” vs. bug
In the Mad magazine comic strip Spy vs. Spy, a pair of sinister-looking agents—one dressed in white, the other in black—constantly compete to come up with clever plots for evading or exterminating each other. Something similar happens in infectious diseases, with invading bacteria or viruses trying to subvert their host’s immune system, and immune system cells employing counter-strategies.
A major player in that intricate interaction is the macrophage (big eater), an amoeba-like white blood cell that crawls around searching for invaders and other particles to ingest, somehow recognizing what it should eat and what it should simply slide over. By looking closely at its biology and chemistry, researchers like Joel Swanson hope to learn exactly how the macrophage operates when it does its job successfully and how disease-causing microbes are sometimes able to exploit the macrophage’s normal processes to gain an advantage.
“A famous scientist I studied with once said to me, ‘We can learn a lot more about infectious disease by studying the macrophage than we can by studying any individual pathogen,’” says Swanson. To that end, his research group builds microscopes and develops techniques for observing and analyzing the chemistry inside living macrophages.
Adam Hoppe, a research investigator who worked with Swanson, invented ways of analyzing digital images from a fluorescence microscope that provide never-before-possible, three-dimensional information about the distribution and abundance of molecules inside macrophages or other cells. “So we now have a tool for looking at host-pathogen interactions in three-dimensions,” says Swanson. Hoppe’s inventions are centerpieces of the Department of Microbiology & Immunology’s recently established Center for Live Cell Imaging.
In one line of work, Swanson’s group has explored what happens when a macrophage swallows up Listeria monocytogenes, a bacterium that is implicated in food poisoning and can cause fever, meningitis and encephalitis. Within a half hour of being taken up and sequestered inside a special compartment in the macrophage, Listeria performs a Houdini act. The wily bug escapes its prison by secreting a protein that dissolves the compartment’s lining. Unless, that is, the macrophage is on the alert, tipped off by signals sent from other immune system cells. In this activated state, the macrophage prevents the captive Listeria from pulling off its escape act.
Recently Swanson and coworkers have begun to focus their attention on interactions between macrophages and Bacillus anthracis, the bacterium that causes anthrax. In collaboration with Microbiology & Immunology associate professor Philip Hanna and professor Marc Peters-Golden in the Department of Internal Medicine, Swanson’s lab is studying how one of the toxins produced by the bug inhibits phagocytosis—the process by which macrophages engulf bacteria. Spying on that interaction and teasing out its details could turn Swanson and associates into counter-agents, devising new strategies to defeat deadly bugs.
