Combined Action of Nucleic Acid-Sensing Toll-like Receptors and TLR11/TLR12 Heterodimers Imparts Resistance to Toxoplasma gondii in Mice

التفاصيل البيبلوغرافية
العنوان: Combined Action of Nucleic Acid-Sensing Toll-like Receptors and TLR11/TLR12 Heterodimers Imparts Resistance to Toxoplasma gondii in Mice
المؤلفون: Kamalpreet Nagpal, Sankar Ghosh, Miriam S. Dutra, Daniella Castanheira Bartholomeu, Espiridion Ramos-Martinez, Ricardo T. Gazzinelli, Douglas T. Golenbock, Mariane B. Melo, Maria do Carmo M. Souza, Warrison A. Andrade
المصدر: Cell Host & Microbe. 13(1):42-53
بيانات النشر: Elsevier BV, 2013.
سنة النشر: 2013
مصطلحات موضوعية: Cancer Research, Microbiology, Article, Host-Parasite Interactions, Proinflammatory cytokine, Mice, Virology, Immunology and Microbiology(all), parasitic diseases, Animals, Humans, Molecular Biology, Disease Resistance, Mice, Knockout, Membrane Glycoproteins, Innate immune system, biology, Toll-Like Receptors, RNA, Toxoplasma gondii, TLR7, DNA, Protozoan, biology.organism_classification, Immunity, Innate, Mice, Inbred C57BL, Toll-Like Receptor 7, Profilin, Toll-Like Receptor 9, TLR3, biology.protein, Nucleic acid, Female, Parasitology, Dimerization, Toxoplasma, RNA, Protozoan, Toxoplasmosis
الوصف: Summary "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 experimental toxoplasmosis. Investigating this further, we found that while parasite RNA and DNA activate innate immune responses via TLR7 and TLR9, 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 proinflammatory 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.
تدمد: 1931-3128
DOI: 10.1016/j.chom.2012.12.003
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::378116cf993363cb5603b7b5b06008fe
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....378116cf993363cb5603b7b5b06008fe
قاعدة البيانات: OpenAIRE
الوصف
تدمد:19313128
DOI:10.1016/j.chom.2012.12.003