TLR11 Activation of Dendritic Cells by a Protozoan Profilin-Like Protein

TLDR

Toll‑like receptors are key innate sensors in dendritic cells, but their role in detecting eukaryotic pathogens remains poorly understood. A profilin‑like protein from *Toxoplasma gondii* activates dendritic cells through TLR11, inducing IL‑12 production and conferring resistance to infection, establishing TLR11 as the first defined ligand for this receptor.

Abstract

Mammalian Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs). Although TLRs are clearly involved in the detection of bacteria and viruses, relatively little is known about their function in the innate response to eukaryotic microorganisms. Here we identify a profilin-like molecule from the protozoan parasite Toxoplasma gondii that generates a potent interleukin-12 (IL-12) response in murine DCs that is dependent on myeloid differentiation factor 88. T. gondii profilin activates DCs through TLR11 and is the first chemically defined ligand for this TLR. Moreover, TLR11 is required in vivo for parasite-induced IL-12 production and optimal resistance to infection, thereby establishing a role for the receptor in host recognition of protozoan pathogens.