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Publication : Alarmin S100A11 initiates a chemokine response to the human pathogen Toxoplasma gondii.

First Author  Safronova A Year  2019
Journal  Nat Immunol Volume  20
Issue  1 Pages  64-72
PubMed ID  30455460 Mgi Jnum  J:282426
Mgi Id  MGI:6380887 Doi  10.1038/s41590-018-0250-8
Citation  Safronova A, et al. (2019) Alarmin S100A11 initiates a chemokine response to the human pathogen Toxoplasma gondii. Nat Immunol 20(1):64-72
abstractText  Toxoplasma gondii is a common protozoan parasite that infects up to one third of the world's population. Notably, very little is known about innate immune sensing mechanisms for this obligate intracellular parasite by human cells. Here, by applying an unbiased biochemical screening approach, we show that human monocytes recognized the presence of T. gondii infection by detecting the alarmin S100A11 protein, which is released from parasite-infected cells via caspase-1-dependent mechanisms. S100A11 induced a potent chemokine response to T. gondii by engaging its receptor RAGE, and regulated monocyte recruitment in vivo by inducing expression of the chemokine CCL2. Our experiments reveal a sensing system for T. gondii by human cells that is based on the detection of infection-mediated release of S100A11 and RAGE-dependent induction of CCL2, a crucial chemokine required for host resistance to the parasite.
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