title: TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection.
abstract: To investigate the role of the Toll-like receptor (TLR) family in host defense against Toxoplasma gondii, we infected TLR2-, TLR4- and MyD88-deficient mice with the avirulent cyst-forming Fukaya strain of T. gondii. All TLR2- and MyD88-deficient mice died within 8 days, whereas all TLR4-deficient and wild-type mice survived after i.p. infection with a high dose of T. gondii. Peritoneal macrophages from T. gondii-infected TLR2- and MyD88-deficient mice did not produce any detectable levels of NO. T. gondii loads in the brain tissues of TLR2- and MyD88-deficient mice were higher than in those of TLR4-deficient and wild-type mice. Furthermore, high levels of IFN-gamma and IL-12 were produced in peritoneal exudate cells (PEC) of TLR4-deficient and wild-type mice after infection, but low levels of cytokines were produced in PEC of TLR2- and MyD88-deficient mice. On the other hand, high levels of IL-4 and IL-10 were produced in PEC of TLR2- and MyD88-deficient mice after infection, but low levels of cytokines were produced in PEC of TLR4-deficient and wild-type mice. The most remarkable histological changes with infiltration of inflammatory cells were observed in lungs of TLR2-deficient mice infected with T. gondii, where severe interstitial pneumonia occurred and abundant T. gondii were found.
authors.affiliation: Department of Infection and Host Defense, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hye-Seong
authors.initials: HS
authors.lastname: Mun
authors.forename: Fumie
authors.initials: F
authors.lastname: Aosai
authors.forename: Kazumi
authors.initials: K
authors.lastname: Norose
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.forename: Lian-Xun
authors.initials: LX
authors.lastname: Piao
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikura
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yano
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D009569:Nitric Oxide / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000276:immunology*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014122:Toxoplasma / Q000276:immunology* / Q000302:isolation & purification; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D019323:omega-N-Methylarginine
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D001120:Arginine; D016207:Cytokines; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D009569:Nitric Oxide; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C507780:Myd88 protein, mouse; C092506:N(G)-monomethylarginine acetate; D019323:omega-N-Methylarginine