Macrophages—immune cells abundant in all body tissues—switch into a different state when a person is infected with parasitic worms, but scientists do not yet know whether these “alternatively activated” macrophages kill the worms, calm the immune system, or repair the tissue damage the worms cause. This matters because the same type of macrophage also appears in chronic diseases such as asthma, lung fibrosis, and cancer, yet its role in those conditions remains unclear. By studying these cells during worm infection—where they presumably evolved to function—the researchers hope to identify which macrophage products might be targeted to treat those chronic diseases. The work could also inform vaccine design against parasitic worms, which cause debilitating infections in millions of people across the tropics. This is primarily fundamental science: it asks basic questions about what a common immune cell does during a natural infection. Understanding that normal function is a necessary first step before any therapeutic application becomes possible. Past discoveries about macrophage biology have already led to treatments for inflammatory diseases, and a clearer picture of alternative activation could open similar avenues.
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Macrophages are cells found in abundance in all tissues of the body that participate in a wide range of essentials functions through their ability to respond to signals in the local environment. T cells, which orchestrate the immune response to infection, are a key source of these signals. In response to microbial infections, T cells produce signals that ?classically-activate? macrophages to become very effective at killing intracellular bacteria. In contrast, when an individual is infected with worms T cells produce signals that ?alternatively-activate? macrophages. The function of alternatively activated macrophages (AAMac) is poorly understood but data suggests they are involved in dampening down inflammation and mediating wound repair. The possibility that they also act as cells that can kill extra-cellular parasites such as worms has not been directly addressed. AAMac have now been found in a variety of chronic disease conditions including asthma, lung fibrosis and cancer but their role has not been clearly defined. We propose to address 1) whether AAMac have direct anti-worm function, 2) whether they induce regulatory pathways associated with chronic infection and 3) whether they mediate repair of wounds caused by tissue-migrating worms. By focussing on the normal function of these cells during worm infection we hope to reveal the appropriate roles of these cells and thus address which of products of AAMac may be useful as targets in treatment of chronic diseases. These studies will also help in the design of vaccines against worms that cause debilitating infections in millions of people in the tropics.
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