Combined action of nucleic acid-sensing Toll-like receptors and TLR11/TLR12 heterodimers imparts resistance to Toxoplasma gondii in mice.
Combined action of nucleic acid-sensing Toll-like receptors and TLR11/TLR12 heterodimers imparts resistance to Toxoplasma gondii in mice.
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DOI：
10.1016/j.chom.2012.12.003
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发表时间：
2013-01-16
影响因子：
30.3
通讯作者：
Gazzinelli RT
中科院分区：
文献类型：
--
作者：
Andrade WA;Souza Mdo C;Ramos-Martinez E;Nagpal K;Dutra MS;Melo MB;Bartholomeu DC;Ghosh S;Golenbock DT;Gazzinelli RT
“Triple-defective” (3d) mice carrying a mutation in UNC93B1, a chaperone for the endosomal nucleic-acid sensing (NAS) Toll-Like Receptors TLR3, TLR7 and TLR9, are highly susceptible to Toxoplasma gondii infection. However, none of the single or even the triple NAS-TLR deficient animals recapitulated the 3d susceptible phenotype to Toxoplasma infection. Investigating this further, we find that while parasite RNA and DNA activate innate immune responses via the NAS-TLRs 7 and 9, TLR11 and TLR12 working as heterodimers are required for sensing and responding to Toxoplasma profilin. Consequently, the triple TLR7/TLR9/TLR11 deficient mice are highly susceptible to T. gondii infection, recapitulating the phenotype of 3d mice. Humans lack functional TLR11 and TLR12 genes. Consistently, human cells produce high levels of pro-inflammatory cytokines in response to parasite derived RNA and DNA, but not to Toxoplasma profilin supporting a more critical role for NAS-TLRs in human toxoplasmosis.
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影响因子：
30.3
作者：
Benson A;Pifer R;Behrendt CL;Hooper LV;Yarovinsky F
通讯作者：
Yarovinsky F
DOI：
10.4049/jimmunol.1003911
发表时间：
2011-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Caetano BC;Carmo BB;Melo MB;Cerny A;dos Santos SL;Bartholomeu DC;Golenbock DT;Gazzinelli RT
通讯作者：
Gazzinelli RT
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
4.4
作者：
Minns, Laurie A.;Menard, Laurence C.;Kasper, Lloyd H.
通讯作者：
Kasper, Lloyd H.
影响因子：
4.4
作者：
Bartholomeu, Daniella C.;Ropert, Catherine;Gazzinelli, Ricardo T.
通讯作者：
Gazzinelli, Ricardo T.