Toxoplasma profilin is essential for host cell invasion and TLR11-dependent induction of an interleukin-12 response.
Apicomplexan parasites exhibit actin-dependent gliding motility that is essential for migration across biological barriers and host cell invasion. Profilins are key contributors to actin polymerization, and the parasite Toxoplasma gondii possesses a profilin-like protein that is recognized by Toll-like receptor TLR11 in the host innate immune system. Here, we show by conditional disruption of the corresponding gene that T.gondii profilin, while not required for intracellular growth, is indispensable for gliding motility, host cell invasion, active egress from host cells, and virulence in mice. Furthermore, parasites lacking profilin are unable to induce TLR11-dependent production in vitro and in vivo of the defensive host cytokine interleukin-12. Thus, profilin is an essential element of two aspects of T. gondii infection. Like bacterial flagellin, profilin plays a role in motility while serving as a microbial ligand recognized by the host innate immune system.
Plattner
Fabienne
F
Department of Microbiology and Molecular Medicine, CMU, University of Geneva, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland.
Yarovinsky
Felix
F
Romero
Stephane
S
Didry
Dominique
D
Carlier
Marie-France
MF
Sher
Alan
A
Soldati-Favre
Dominique
D
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D017125:Genes, Protozoan; D005816:Genetic Complementation Test; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D010963:Plasmodium falciparum / Q000235:genetics; D017354:Point Mutation; D051304:Profilins / Q000502:physiology*; D015800:Protozoan Proteins / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism*; D014122:Toxoplasma / Q000472:pathogenicity* / Q000502:physiology*; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology*; D014774:Virulence
D000199:Actins; D051304:Profilins; D015800:Protozoan Proteins; C482903:Tlr11 protein, mouse; D051193:Toll-Like Receptors; D018664:Interleukin-12