TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection.
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.
Mun
Hye-Seong
HS
Department of Infection and Host Defense, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Aosai
Fumie
F
Norose
Kazumi
K
Chen
Mei
M
Piao
Lian-Xun
LX
Takeuchi
Osamu
O
Akira
Shizuo
S
Ishikura
Hiroshi
H
Yano
Akihiko
A
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
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