One major cause of illness from food-borne diseases is the parasite Toxoplasma gondii (T. gondii). New insights into how the immune system combats T. gondii are provided in a study published by Cell Press Dec. 13th in the journal Immunity. The findings could lead to the development of long-sought vaccines to protect against T. gondii and related parasites.
To fight off pathogens, the immune system relies on Toll-like receptors (TLRs) -- a class of proteins that recognize microbes and activate immune responses. The important role of TLR11 in recognizing the T. gondii infection was previously demonstrated by a team led by Sankar Ghosh of Columbia University and Alan Sher of the National Institute of Allergy and Infectious Diseases. But scientists had not yet identified any TLRs -- including TLR11 -- that could promote survival in infected animals.
In the new study, Ghosh, Sher, and their collaborators focused on the previously uncharacterized TLR12 because it is closely related to TLR11 and physically interacts with that receptor, suggesting that the two might work together to mount immune responses. When they genetically engineered mice to lack TLR12, they found that immune cells could not recognize or protect against T. gondii, and these mice quickly succumbed to infection. Although both TLR11 and TLR12 activate overlapping immune responses to T. gondii in certain types of cells, TLR12 also triggers responses in a distinct set of immune cells to promote survival.
"Prior to this study, TLR12 had no known function in the immune system, and it was not known what pathogen this receptor recognized," Ghosh says. "We have demonstrated that TLR12 is essential for resistance to T. gondii in mice."
Because TLR12 also recognized another related parasite, the findings could have broad clinical implications. "By investigating how immune cells expressing TLR12 organize the immune response against T. gondii infection, we hope to identify new means of promoting protective immune responses against T. gondii and potentially other important parasite pathogens," Ghosh says.
- A. Alicia Koblansky, Dragana Jankovic, Hyunju Oh, Sara Hieny, Waradon Sungnak, Ramkumar Mathur, Matthew S. Hayden, Shizuo Akira, Alan Sher, Sankar Ghosh. Recognition of Profilin by Toll-like Receptor 12 Is Critical for Host Resistance to Toxoplasma gondii. Immunity, 2012; DOI: 10.1016/j.immuni.2012.09.016
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