Summer 2007
Leishmaniasis and Toxoplasmosis Share a Link
Leishmaniasis and toxoplasmosis have more in common than tongue-twisting names. Transmitted by the bite of tiny sand-colored flies, leishmania parasites can cause sores—especially on the face and hands—that take months to heal and that can leave permanent scars. Toxoplasma gondii parasites rarely cause illness in healthy individuals, but people with compromised immune systems or fetuses exposed to the parasite may suffer severe eye and brain damage. Now, NIAID scientists David Sacks, Ph.D., and Alan Sher, Ph.D., and their colleagues have found that both kinds of parasites evoke a common response from the immune system. Specifically, the parasites prompt T helper 1 (Th1) immune cells to undergo a kind of midlife career change that enables them to control their own activity.
The defining trait of Th1 cells is that they make interferon gamma (IFN-gamma), a chemical that ramps up infection-clearing inflammatory responses by arming other immune system cells to kill the parasites. In the face of leishmania or toxoplasma parasites, the researchers discovered, Th1 cells can produce not only IFN-gamma but also another chemical, IL-10. One of the most important “brakes” in the immune system, IL-10 suppresses infection-induced inflammation, in part by counteracting IFN-gamma’s effects. This action prevents the tissue damage that would result from unchecked inflammation. Until now, scientists believed that IL-10 production was restricted to those immune cells that do not secrete IFN-gamma themselves.
Surprisingly, however, Dr. Sher and his coworkers found that a population of IFN-gamma-producing Th1 cells is also the main source of IL-10 in a mouse model of toxoplasmosis. Essentially, the same cells that fight the parasites by releasing IFN-gamma also serve as regulators of that inflammatory response through their production of IL-10. Importantly, the secretion of these two chemicals by Th1 cells involves distinct mechanisms: IFN-gamma secretion is continuous, while IL-10 is produced fleetingly.
In their experiments, Dr. Sacks and his co-investigators used a strain of leishmaniasis parasites that establish non-healing skin lesions in mice. They showed that Th1 cells also simultaneously produce IFN-gamma and IL-10. Unluckily for people with leishmaniasis, IL-10’s anti-inflammatory action allows the parasites to avoid elimination and produce chronic disease. IL-10-producing Th1 cells may also be important in establishing and maintaining other chronic infectious diseases, such as tuberculosis, the scientists note.
—Anne A. Oplinger
References
Anderson, C. F. et al. CD4+CD25-Foxp3- Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. The Journal of Experimental Medicine 204:285-97. DOI:10.1084/jem.20061886 (2007).
Jankovic, D. et al. Conventional T-bet+Foxp3- Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. The Journal of Experimental Medicine 204:273-83. DOI: 10.1084/jem.20062175 (2007).
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