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

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 have identified that human monocytes recognized the presence of T. gondii infection via detection of 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 via engagement of its receptor RAGE and regulated monocyte recruitment in vivo by inducing expression of the chemokine CCL2. Our experiments have revealed a sensing system for T. gondii by human cells that is based on detection infection-mediated release of alarmin S100A11 and RAGE-dependent induction of CCL2, a crucial chemokine required for host resistance to the parasite.