TY - JOUR
T1 - Toxoplasma Profilin Is Essential for Host Cell Invasion and TLR11-Dependent Induction of an Interleukin-12 Response
AU - Plattner, Fabienne
AU - Yarovinsky, Felix
AU - Romero, Stephane
AU - Didry, Dominique
AU - Carlier, Marie France
AU - Sher, Alan
AU - Soldati-Favre, Dominique
N1 - Funding Information:
We thank Dr. Bernardo Foth for assistance with the phylogenetic analysis, Dr. Paco Pino and Noelle Jemmely for cloning PfPRF cDNA and for the generation of anti-PfPRF antibodies. Dr. Herm-Goetz for cloning TgGAP45 cDNA and for the generation of anti-TgGAP45 antibodies. We are grateful to Dr. M.F. Cesbron and Dr. J.F. Dubremetz for providing other antibodies and to Dr. Michael Shea for critical reading of the manuscript. This work is supported by the Swiss National Foundation FN 3100A0-102255/DS and currently 3100A0-116722/DS. It is part of the activities of the BioMalPar European Network of Excellence supported by a European grant (LSHP-CT-2004-503578) from the Priority 1 “Life Sciences, Genomics and Biotechnology for Health” in the 6th Framework Programme, and D.S. is an international scholar of the Howard Hughes Medical Institutes. M.F.C. is supported by “Ligue Nationale contre le Cancer” of HFSP RGP72/2003-C and Europeean STREP “BIOMICS.” The project was also partially funded by the intramural research program of the National Institute of Allergy and Infectious Diseases (NIH).
PY - 2008/2/14
Y1 - 2008/2/14
N2 - 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.
AB - 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.
KW - CELLBIO
KW - MICROBIO
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=38849095132&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38849095132&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2008.01.001
DO - 10.1016/j.chom.2008.01.001
M3 - Article
C2 - 18312842
AN - SCOPUS:38849095132
SN - 1931-3128
VL - 3
SP - 77
EP - 87
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 2
ER -