The role of Toll-like receptors (TLRs) in stroke

References

Aalaei-andabili, S.H. and Rezaei, N. (2013). Toll like receptor (TLR)-induced differential expression of microRNAs (MiRs) promotes proper immune response against infections: a systematic review. J. Infect. 67, 251–264.10.1016/j.jinf.2013.07.016Search in Google Scholar PubMed

Aderem, A. and Ulevitch, R.J. (2000). Toll-like receptors in the induction of the innate immune response. Nature 406, 782–787.10.1038/35021228Search in Google Scholar PubMed

Akira, S. and Takeda, K. (2004). Toll-like receptor signalling. Nat. Rev. Immunol. 4, 499–511.10.1038/nri1391Search in Google Scholar PubMed

Akira, S., Uematsu, S., and Takeuchi, O. (2006). Pathogen recognition and innate immunity. Cell 124, 783–801.10.1016/j.cell.2006.02.015Search in Google Scholar PubMed

Aravalli, R.N., Hu, S., and Lokensgard, J.R. (2008). Inhibition of toll-like receptor signaling in primary murine microglia. J. Neuroimmune Pharmacol. 3, 5–11.10.1007/s11481-007-9097-8Search in Google Scholar PubMed PubMed Central

Babcock, A.A., Wirenfeldt, M., Holm, T., Nielsen, H.H., Dissing-Olesen, L., Toft-Hansen, H., Millward, J.M., Landmann, R., Rivest, S., Finsen, B., et al. (2006). Toll-like receptor 2 signaling in response to brain injury: an innate bridge to neuroinflammation. J. Neurosci. 26, 12826–12837.10.1523/JNEUROSCI.4937-05.2006Search in Google Scholar PubMed PubMed Central

Babcock, A.A., Toft-Hansen, H., and Owens. T. (2008). Signaling through MyD88 regulates leukocyte recruitment after brain injury. J. Immunol. 181, 6481–6490.10.4049/jimmunol.181.9.6481Search in Google Scholar PubMed

Bahjat, F.R., Gesuete, R., and Stenzel-Poore, M.P. (2013). Steps to translate preconditioning from basic research to the clinic. Transl. Stroke Res. 4, 89–103.10.1007/s12975-012-0223-4Search in Google Scholar PubMed PubMed Central

Baldwin, A.S. Jr. (1996). The NF-kappaB and IkappaB proteins: new discoveries and insights. Annu. Rev. Immunol. 14, 649–683.10.1146/annurev.immunol.14.1.649Search in Google Scholar PubMed

Barton, G.M. and Medzhitov, R. (2003). Toll-like receptor signaling pathways. Science 300, 1524–1525.10.1126/science.1085536Search in Google Scholar PubMed

Becker, K.J., Kindrick, D.L., Lester, M.P., Shea, C., and Ye, Z.C. (2005). Sensitization to brain antigens after stroke is augmented by lipopolysaccharide. J. Cereb. Blood Flow Metab. 25, 1634–1644.10.1038/sj.jcbfm.9600160Search in Google Scholar PubMed PubMed Central

Boonstra, A., Rajsbaum, R., Holman, M., Marques, R., Asselin-Paturel, C., Pereira, J.P., Bates, E.E., Akira, S., Vieira, P., Liu, Y.J., et al. (2006). Macrophages and myeloid dendritic cells, but not plasmacytoid dendritic cells, produce IL-10 in response to MyD88- and TRIF-dependent TLR signals, and TLR-independent signals. J. Immunol. 177, 7551–7558.10.4049/jimmunol.177.11.7551Search in Google Scholar PubMed

Brea, D., Sobrino, T., Rodríguez-Yáñez, M., Ramos-Cabrer, P., Agulla, J., Rodríguez-González, R., Campos, F., Blanco, M., and Castillo, J. (2011). Toll-like receptors 7 and 8 expression is associated with poor outcome and greater inflammatory response in acute ischemic stroke. Clin. Immunol. 139, 193–198.10.1016/j.clim.2011.02.001Search in Google Scholar PubMed

Broad, A., Kirby, J.A., and Jones, D.E., Applied Immunology and Transplantation Research Group (2007). Toll-like receptor interactions: tolerance of MyD88-dependent cytokines but enhancement of MyD88-independent interferon-beta production. Immunology 120, 103–111.10.1111/j.1365-2567.2006.02485.xSearch in Google Scholar PubMed PubMed Central

Buchanan, M.M., Hutchinson, M., Watkins, L.R., and Yin, H. (2010). Toll-like receptor 4 in CNS pathologies. J. Neurochem. 114, 13–27.10.1111/j.1471-4159.2010.06736.xSearch in Google Scholar PubMed PubMed Central

Cao, C.X., Yang, Q.W., Lv, F.L., Cui, J., Fu, H.B., and Wang, J.Z. (2007). Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice. Biochem. Biophys. Res. Commun. 353, 509–514.10.1016/j.bbrc.2006.12.057Search in Google Scholar PubMed

Carty, M. and Bowie, A.G. (2011). Evaluating the role of Toll-like receptors in diseases of the central nervous system. Biochem. Pharmacol. 81, 825–837.10.1016/j.bcp.2011.01.003Search in Google Scholar PubMed

Caso, J.R., Pradillo, J.M., Hurtado, O., Lorenzo, P., Moro, M.A., and Lizasoain, I. (2007). Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation 115, 1599–1608.10.1161/CIRCULATIONAHA.106.603431Search in Google Scholar PubMed

Cusson-Hermance, N., Khurana, S., Lee, T.H., Fitzgerald, K.A., and Kelliher, M.A. (2005). Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-kappaB activation but does not contribute to interferon regulatory factor 3 activation. J. Biol. Chem. 280, 36560–36566.10.1074/jbc.M506831200Search in Google Scholar PubMed

Dalpke, A.H., Lehner, M.D., Hartung, T., and Heeg, K. (2005). Differential effects of CpG-DNA in Toll-like receptor-2/-4/-9 tolerance and cross-tolerance. Immunology 116, 203–212.10.1111/j.1365-2567.2005.02211.xSearch in Google Scholar PubMed PubMed Central

Deng, L., Wang, C., Spencer, E., Yang, L., Braun, A., You, J., Slaughter, C., Pickart, C., and Chen, Z.J. (2000). Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103, 351–361.10.1016/S0092-8674(00)00126-4Search in Google Scholar

Downes, C.E. and Crack, P.J. (2010). Neural injury following stroke: are Toll-like receptors the link between the immune system and the CNS? Br. J. Pharmacol. 160, 1872–1888.10.1111/j.1476-5381.2010.00864.xSearch in Google Scholar

Downes, C.E., Wong, C.H., Henley, K.J., Guio-Aguilar, P.L., Zhang, M., Ates, R., Mansell, A., Kile, B.T., and Crack, P.J. (2013). MyD88 is a critical regulator of hematopoietic cell-mediated neuroprotection seen after stroke. PLoS One 8, e57948.10.1371/journal.pone.0057948Search in Google Scholar

Famakin, B.M., Mou, Y., Ruetzler, C.A., Bembry, J., Maric, D., and Hallenbeck, J.M. (2011). Disruption of downstream MyD88 or TRIF Toll-like receptor signaling does not protect against cerebral ischemia. Brain Res. 1388, 148–156.10.1016/j.brainres.2011.02.074Search in Google Scholar

Ferronato, S., Lira, M.G., Olivato, S., Scuro, A., Veraldi, G.F., Romanelli, M.G., Patuzzo, C., Malerba, G., Pignatti, P.F., and Mazzucco, S. (2011). Upregulated expression of Toll-like receptor 4 in peripheral blood of ischaemic stroke patients correlates with cyclooxygenase 2 expression. Eur. J. Vasc. Endovasc. Surg. 41, 358–363.10.1016/j.ejvs.2010.11.019Search in Google Scholar

Grilli, M., Barbieri, I., Basudev, H., Brusa, R., Casati, C., Lozza, G., and Ongini, E. (2000). Interleukin-10 modulates neuronal threshold of vulnerability to ischaemic damage. Eur. J. Neurosci. 12, 2265–2272.10.1046/j.1460-9568.2000.00090.xSearch in Google Scholar

Guha, M. and Mackman, N. (2001). LPS induction of gene expression in human monocytes. Cell Signal. 13, 85–94.10.1016/S0898-6568(00)00149-2Search in Google Scholar

Hayashi, F., Smith, K.D., Ozinsky, A., Hawn, T.R., Yi, E.C., Goodlett, D.R., Eng, J.K., Akira, S., Underhill, D.M., and Aderem, A. (2001). The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099–1103.10.1038/35074106Search in Google Scholar

Hedayat, M., Netea, M.G., and Rezaei, N. (2011). Targeting of Toll-like receptors: a decade of progress in combating infectious diseases. Lancet Infect. Dis. 11, 702–712.10.1016/S1473-3099(11)70099-8Search in Google Scholar

Hedayat, M., Takeda, K., and Rezaei, N. (2012). Prophylactic and therapeutic implications of toll-like receptor ligands. Med. Res. Rev. 32, 294–325.10.1002/med.20214Search in Google Scholar PubMed

Heiss, W.D. (2012). The ischemic penumbra: how does tissue injury evolve? Ann. N. Y. Acad. Sci. 1268, 26–34.10.1111/j.1749-6632.2012.06668.xSearch in Google Scholar PubMed

Hickey, E.J., You, X., Kaimaktchiev, V., Stenzel-Poore, M., and Ungerleider, R.M. (2007). Lipopolysaccharide preconditioning induces robust protection against brain injury resulting from deep hypothermic circulatory arrest. J. Thorac. Cardiovasc. Surg. 133, 1588–1596.10.1016/j.jtcvs.2006.12.056Search in Google Scholar PubMed

Hochrein, H., Schlatter, B., O’Keeffe, M., Wagner, C., Schmitz, F., Schiemann, M., Bauer, S., Suter, M., and Wagner, H. (2004). Herpes simplex virus type-1 induces IFN-alpha production via Toll-like receptor 9-dependent and -independent pathways. Proc. Natl. Acad. Sci. USA 101, 11416–11421.10.1073/pnas.0403555101Search in Google Scholar PubMed PubMed Central

Hoebe, K., Du, X., Georgel, P., Janssen, E., Tabeta, K., Kim, S.O., Goode, J., Lin, P., Mann, N., Mudd, S., et al. (2003). Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424, 743–748.10.1038/nature01889Search in Google Scholar PubMed

Hua, F., Ha, T., Ma, J., Gao, X., Kelley, J., Williams, D.L., Browder, I.W., Kao, R.L., and Li, C. (2005). Blocking the MyD88-dependent pathway protects the myocardium from ischemia/reperfusion injury in rat hearts. Biochem. Biophys. Res. Commun. 338, 1118–1125.10.1016/j.bbrc.2005.10.068Search in Google Scholar PubMed

Hua, F., Ma, J., Ha, T., Xia, Y., Kelley, J., Williams, D.L., Kao, R.L., Browder, I.W., Schweitzer, J.B., Kalbfleisch, J.H., et al. (2007). Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusion. J. Neuroimmunol. 190, 101–111.10.1016/j.jneuroim.2007.08.014Search in Google Scholar PubMed PubMed Central

Hua, F., Ma, J., Ha, T., Kelley, J.L., Kao, R.L., Schweitzer, J.B., Kalbfleisch, J.H., Williams, D.L., and Li, C. (2009a). Differential roles of TLR2 and TLR4 in acute focal cerebral ischemia/reperfusion injury in mice. Brain Res. 1262, 100–108.10.1016/j.brainres.2009.01.018Search in Google Scholar PubMed PubMed Central

Hua, F., Wang, J., Sayeed, I., Ishrat, T., Atif, F., and Stein, D.G. (2009b). The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice. Biochem. Biophys. Res. Commun. 390, 678–683.10.1016/j.bbrc.2009.10.027Search in Google Scholar PubMed PubMed Central

Hurn, P.D., Subramanian, S., Parker, S.M., Afentoulis, M.E., Kaler, L.J., Vandenbark, A.A., and Offner, H. (2007). T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J. Cereb. Blood Flow Metab. 27, 1798–1805.10.1038/sj.jcbfm.9600482Search in Google Scholar PubMed PubMed Central

Hyakkoku, K., Hamanaka, J., Tsuruma, K., Shimazawa, M., Tanaka, H., Uematsu, S., Akira, S., Inagaki, N., Nagai, H., and Hara, H. (2010). Toll-like receptor 4 (TLR4), but not TLR3 or TLR9, knock-out mice have neuroprotective effects against focal cerebral ischemia. Neuroscience 171, 258–267.10.1016/j.neuroscience.2010.08.054Search in Google Scholar PubMed

Iadecola, C. and Anrather, J. (2011). The immunology of stroke: from mechanisms to translation. Nat. Med. 17, 796–808.10.1038/nm.2399Search in Google Scholar PubMed PubMed Central

Jauch, E.C., Lindsell, C., Broderick, J., Fagan, S.C., Tilley, B.C., and Levine, S.R., NINDS rt-PA Stroke Study Group (2006). Association of serial biochemical markers with acute ischemic stroke: the National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study. Stroke 37, 2508–2513.10.1161/01.STR.0000242290.01174.9eSearch in Google Scholar PubMed

Jiang, Z., Mak, T.W., Sen, G., and Li, X. (2004). Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-beta. Proc. Natl. Acad. Sci. USA 101, 3533–3538.10.1073/pnas.0308496101Search in Google Scholar PubMed PubMed Central

Jiang, D., Liang, J., Fan, J., Yu, S., Chen, S., Luo, Y., Prestwich, G.D., Mascarenhas, M.M., Garg, H.G., Quinn, D.A., et al. (2005). Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat. Med. 11, 1173–1179.10.1038/nm1315Search in Google Scholar PubMed

Johnson, G.B., Brunn, G.J., Kodaira, Y., and Platt, J.L. (2002). Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4. J. Immunol. 168, 5233–5239.10.4049/jimmunol.168.10.5233Search in Google Scholar PubMed

Johnson, T.V., Camras, C.B., and Kipnis, J. (2007). Bacterial DNA confers neuroprotection after optic nerve injury by suppressing CD4⁺CD25⁺ regulatory T-cell activity. Invest. Ophthalmol. Vis. Sci. 48, 3441–3449.10.1167/iovs.06-1351Search in Google Scholar PubMed

Jung, D.Y., Lee, H., Jung, B.Y., Ock, J., Lee, M.S., Lee, W.H., and Suk, K. (2005). TLR4, but not TLR2, signals autoregulatory apoptosis of cultured microglia: a critical role of IFN-beta as a decision maker. J. Immunol. 174, 6467–6476.10.4049/jimmunol.174.10.6467Search in Google Scholar PubMed

Kariko, K., Ni, H., Capodici, J., Lamphier, M., and Weissman. D. (2004). mRNA is an endogenous ligand for Toll-like receptor 3. J. Biol. Chem. 279, 12542–12550.10.1074/jbc.M310175200Search in Google Scholar PubMed

Kawai, T. and Akira, S. (2007a). Signaling to NF-kappaB by Toll-like receptors. Trends Mol. Med. 13, 460–469.10.1016/j.molmed.2007.09.002Search in Google Scholar PubMed

Kawai, T. and Akira, S. (2007b). TLR signaling. Semin. Immunol. 19, 24–32.10.1016/j.smim.2006.12.004Search in Google Scholar PubMed

Kawai, T. and Akira, S. (2009). The roles of TLRs, RLRs and NLRs in pathogen recognition. Int. Immunol. 21, 317–337.10.1093/intimm/dxp017Search in Google Scholar

Kawai, T., Adachi, O., Ogawa, T., Takeda, K., and Akira, S. (1999). Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11, 115–122.10.1016/S1074-7613(00)80086-2Search in Google Scholar

Kawai, T., Sato, S., Ishii, K.J., Coban, C., Hemmi, H., Yamamoto, M., Terai, K., Matsuda, M., Inoue, J., Uematsu, S., et al. (2004). Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat. Immunol. 5, 1061–1068.10.1038/ni1118Search in Google Scholar PubMed

Keller, J.N., Pang, Z., Geddes, J.W., Begley, J.G., Germeyer, A., Waeg, G., and Mattson, M.P. (1997). Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid beta-peptide: role of the lipid peroxidation product 4-hydroxynonenal. J. Neurochem. 69, 273–284.10.1046/j.1471-4159.1997.69010273.xSearch in Google Scholar PubMed

Kissler, S., Anderton, S.M., and Wraith, D.C. (2001). Antigen-presenting cell activation: a link between infection and autoimmunity? J. Autoimmun. 16, 303–308.10.1006/jaut.2000.0498Search in Google Scholar PubMed

Koedel, U., Merbt, U.M., Schmidt, C., Angele, B., Popp, B., Wagner, H., Pfister, H.W., and Kirschning, C.J. (2007). Acute brain injury triggers MyD88-dependent, TLR2/4-independent inflammatory responses. Am. J. Pathol. 171, 200–213.10.2353/ajpath.2007.060821Search in Google Scholar PubMed PubMed Central

Krutzik, S.R., Ochoa, M.T., Sieling, P.A., Uematsu, S., Ng, Y.W., Legaspi, A., Liu, P.T., Cole, S.T., Godowski, P.J., Maeda, Y., et al. (2003). Activation and regulation of Toll-like receptors 2 and 1 in human leprosy. Nat. Med. 9, 525–532.10.1038/nm864Search in Google Scholar PubMed

Lau, C.M., Broughton, C., Tabor, A.S., Akira, S., Flavell, R.A., Mamula, M.J., Christensen, S.R., Shlomchik, M.J., Viglianti, G.A., Rifkin, I.R., et al. (2005). RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement. J. Exp. Med. 202, 1171–1177.10.1084/jem.20050630Search in Google Scholar PubMed PubMed Central

Leadbetter, E.A., Rifkin, I.R., Hohlbaum, A.M., Beaudette, B.C., Shlomchik, M.J., and Marshak-Rothstein, A. (2002). Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 416, 603–607.10.1038/416603aSearch in Google Scholar PubMed

Lehnardt, S., Lehmann, S., Kaul, D., Tschimmel, K., Hoffmann, O., Cho, S., Krueger, C., Nitsch, R., Meisel, A., and Weber, J.R. (2007). Toll-like receptor 2 mediates CNS injury in focal cerebral ischemia. J. Neuroimmunol. 190, 28–33.10.1016/j.jneuroim.2007.07.023Search in Google Scholar PubMed

Lehnardt, S., Schott, E., Trimbuch, T., Laubisch, D., Krueger, C., Wulczyn, G., Nitsch, R., and Weber, J.R. (2008). A vicious cycle involving release of heat shock protein 60 from injured cells and activation of toll-like receptor 4 mediates neurodegeneration in the CNS. J. Neurosci. 28, 2320–2331.10.1523/JNEUROSCI.4760-07.2008Search in Google Scholar PubMed PubMed Central

Leung, P.Y., Stevens, S.L., Packard, A.E., Lessov, N.S., Yang, T., Conrad, V.K., van den Dungen, N.N., Simon, R.P., and Stenzel-Poore, M.P. (2012). Toll-like receptor 7 preconditioning induces robust neuroprotection against stroke by a novel type I interferon-mediated mechanism. Stroke 43, 1383–1389.10.1161/STROKEAHA.111.641522Search in Google Scholar PubMed PubMed Central

Liesz, A., Suri-Payer, E., Veltkamp, C., Doerr, H., Sommer, C., Rivest, S., Giese, T., and Veltkamp, R. (2009). Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat. Med. 15, 192–199.10.1038/nm.1927Search in Google Scholar PubMed

Marsh, B., Stevens, S.L., Packard, A.E.B., Gopalan, B., Hunter, B., Leung, P.Y., Harrington, C.A., and Stenzel-Poore, M.P. (2009). Systemic lipopolysaccharide protects the brain from ischemic injury by reprogramming the response of the brain to stroke: a critical role for IRF3. J. Neurosci. 29, 9839–9849.10.1523/JNEUROSCI.2496-09.2009Search in Google Scholar PubMed PubMed Central

Marta, M., Andersson, A., Isaksson, M., Kämpe, O., and Lobell, A. (2008). Unexpected regulatory roles of TLR4 and TLR9 in experimental autoimmune encephalomyelitis. Eur. J. Immunol. 38, 565–575.10.1002/eji.200737187Search in Google Scholar PubMed

Miggin, S.M. and O’Neill, L.A. (2006). New insights into the regulation of TLR signaling. J. Leukoc. Biol. 80, 220–226.10.1189/jlb.1105672Search in Google Scholar PubMed

Moghimpour Bijani, F., Vallejo, J.G., and Rezaei, N. (2012). Toll-like receptor signaling pathways in cardiovascular diseases: challenges and opportunities. Int. Rev. Immunol. 31, 379–395.10.3109/08830185.2012.706761Search in Google Scholar PubMed

Moossavi, S. and Rezaei, N. (2012). Toll-like receptor expression pattern: clinical application. J. Clin. Immunol. 32, 1421–1422.10.1007/s10875-012-9719-7Search in Google Scholar PubMed

Moossavi, S. and Rezaei, N. (2013). Toll-like receptor signalling and their therapeutic targeting in colorectal cancer. Int. Immunopharmacol. 16, 199–209.10.1016/j.intimp.2013.03.017Search in Google Scholar PubMed

Moskowitz, M.A., Lo, E.H., and Iadecola, C. (2010). The science of stroke: mechanisms in search of treatments. Neuron 67, 181–198.10.1016/j.neuron.2010.07.002Search in Google Scholar PubMed PubMed Central

Nathan, C. and Ding, A. (2010). Nonresolving inflammation. Cell 140, 871–882.10.1016/j.cell.2010.02.029Search in Google Scholar PubMed

Ninomiya-Tsuji, J., Kishimoto, K., Hiyama, A., Inoue J., Cao, Z., and Matsumoto, K. (1999). The kinase TAK1 can activate the NIK-IkappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 398, 252–256.10.1038/18465Search in Google Scholar PubMed

O’Neill, L.A. (2006). How Toll-like receptors signal: what we know and what we don’t know. Curr. Opin. Immunol. 18, 3–9.10.1016/j.coi.2005.11.012Search in Google Scholar PubMed

Ohashi, K., Burkart, V., Flohé, S., and Kolb, H. (2000). Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J. Immunol. 164, 558–561.10.4049/jimmunol.164.2.558Search in Google Scholar PubMed

Okun, E., Griffioen, K.J., Lathia, J.D., Tang, S.C., Mattson, M.P., and Arumugam, T.V. (2009). Toll-like receptors in neurodegeneration. Brain Res. Rev. 59, 278–292.10.1016/j.brainresrev.2008.09.001Search in Google Scholar PubMed PubMed Central

Ozinsky, A., Underhill, D.M., Fontenot, J.D., Hajjar, A.M., Smith, K.D., Wilson, C.B., Schroeder, L., and Aderem, A. (2000). The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc. Natl. Acad. Sci. USA 97, 13766–13771.10.1073/pnas.250476497Search in Google Scholar PubMed PubMed Central

Pais, T.F., Figueiredo, C., Peixoto, R., Braz, M.H., and Chatterjee, S. (2008). Necrotic neurons enhance microglial neurotoxicity through induction of glutaminase by a MyD88-dependent pathway. J. Neuroinflamm. 5, 43.10.1186/1742-2094-5-43Search in Google Scholar PubMed PubMed Central

Pasare, C. and Medzhitov, R. (2005). Toll-like receptors: linking innate and adaptive immunity. Adv. Exp. Med. Biol. 560, 11–18.10.1007/0-387-24180-9_2Search in Google Scholar PubMed

Piao, W., Song, C., Chen, H., Diaz, M.A., Wahl, L.M., Fitzgerald, K.A., Li, L., and Medvedev, A.E. (2009). Endotoxin tolerance dysregulates MyD88- and Toll/IL-1R domain-containing adapter inducing IFN-beta-dependent pathways and increases expression of negative regulators of TLR signaling. J. Leukoc. Biol. 86, 863–875.10.1189/jlb.0309189Search in Google Scholar PubMed PubMed Central

Poikonen, K., Lajunen, T., Silvennoinen-Kassinen, S., Leinonen, M., and Saikku, P. (2009). Effects of CD14, TLR2, TLR4, LPB, and IL-6 gene polymorphisms on Chlamydia pneumoniae growth in human macrophages in vitro. Scand. J. Immunol. 70, 34–39.10.1111/j.1365-3083.2009.02267.xSearch in Google Scholar PubMed

Pradillo, J.M., Fernandez-Lopez, D., García-Yébenes, I., Sobrado, M., Hurtado, O., Moro, M.A., and Lizasoain, I. (2009). Toll-like receptor 4 is involved in neuroprotection afforded by ischemic preconditioning. J. Neurochem. 109, 287–294.10.1111/j.1471-4159.2009.05972.xSearch in Google Scholar PubMed

Prass, K., Braun, J.S., Dirnagl, U., Meisel, C., and Meisel, A. (2006). Stroke propagates bacterial aspiration to pneumonia in a model of cerebral ischemia. Stroke 37, 2607–2612.10.1161/01.STR.0000240409.68739.2bSearch in Google Scholar PubMed

Prinz, M., Garbe, F., Schmidt, H., Mildner, A., Gutcher, I., Wolter, K., Piesche, M., Schroers, R., Weiss, E., Kirschning, C.J., et al. (2006). Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of multiple sclerosis. J. Clin. Invest. 116, 456–464.10.1172/JCI26078Search in Google Scholar PubMed PubMed Central

Qiu, J., Xu, J., Zheng, Y., Wei, Y., Zhu, X., Lo, E.H., Moskowitz, M.A., and Sims, J.R. (2010). High-mobility group box 1 promotes metalloproteinase-9 upregulation through Toll-like receptor 4 after cerebral ischemia. Stroke 41, 2077–2082.10.1161/STROKEAHA.110.590463Search in Google Scholar PubMed PubMed Central

Rezaei, N. (2006). Therapeutic targeting of pattern-recognition receptors. Int. Immunopharmacol. 6, 863–869.10.1016/j.intimp.2006.02.005Search in Google Scholar PubMed

Rosenzweig, H.L., Minami, M., Lessov, N.S., Coste, S.C., Stevens, S.L., Henshall, D.C., Meller, R., Simon, R.P., and Stenzel-Poore, M.P. (2007). Endotoxin preconditioning protects against the cytotoxic effects of TNFalpha after stroke: a novel role for TNFalpha in LPS-ischemic tolerance. J. Cereb. Blood Flow Metab. 27, 1663–1674.10.1038/sj.jcbfm.9600464Search in Google Scholar PubMed

Samarasinghe, R., Tailor, P., Tamura, T., Kaisho, T., Akira, S., and Ozato, K. (2006). Induction of an anti-inflammatory cytokine, IL-10, in dendritic cells after toll-like receptor signaling. J. Interferon Cytokine Res. 26, 893–900.10.1089/jir.2006.26.893Search in Google Scholar PubMed

Schwartz, M. and Kipnis, J. (2005). Protective autoimmunity and neuroprotection in inflammatory and noninflammatory neurodegenerative diseases. J. Neurol. Sci. 233, 163–166.10.1016/j.jns.2005.03.014Search in Google Scholar PubMed

Shichita, T., Ago, T., Kamouchi, M., Kitazono, T., Yoshimura, A., and Ooboshi, H. (2012a). Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke. J. Neurochem. 123(Suppl 2), 29–38.10.1111/j.1471-4159.2012.07941.xSearch in Google Scholar PubMed

Shichita, T., Hasegawa, E., Kimura, A., Morita, R., Sakaguchi, R., Takada, I., Sekiya, T., Ooboshi, H., Kitazono, T., Yanagawa, T., et al. (2012b). Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain. Nat. Med. 18, 911–917.10.1038/nm.2749Search in Google Scholar PubMed

Shimazu, R., Akashi, S., Ogata, H., Nagai, Y., Fukudome, K., Miyake, K., and Kimoto, M. (1999). MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189, 1777–1782.10.1084/jem.189.11.1777Search in Google Scholar

Stevens, S.L., Ciesielski, T.M., Marsh, B.J., Yang, T., Homen, D.S., Boule, J.L., Lessov, N.S., Simon, R.P., and Stenzel-Poore, M.P. (2008). Toll-like receptor 9: a new target of ischemic preconditioning in the brain. J. Cereb. Blood Flow Metab. 28, 1040–1047.10.1038/sj.jcbfm.9600606Search in Google Scholar

Stevens, S.L., Leung, P.Y., Vartanian, K.B., Gopalan, B., Yang, T., Simon, R.P., and Stenzel-Poore, M.P. (2011). Multiple preconditioning paradigms converge on interferon regulatory factor-dependent signaling to promote tolerance to ischemic brain injury. J. Neurosci. 31, 8456–8463.10.1523/JNEUROSCI.0821-11.2011Search in Google Scholar

Takaoka, A., Yanai, H., Kondo, S., Duncan, G., Negishi, H., Mizutani, T., Kano, S., Honda, K., Ohba, Y., Mak, T.W., et al. (2005). Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 434, 243–249.10.1038/nature03308Search in Google Scholar

Takeda, K., Kaisho, T., and Akira, S. (2003). Toll-like receptors. Annu. Rev. Immunol. 21, 335–376.10.1146/annurev.immunol.21.120601.141126Search in Google Scholar

Tang, S.C., Arumugam, T.V., Xu, X., Cheng, A., Mughal, M.R., Jo, D.G., Lathia, J.D., Siler, D.A., Chigurupati, S., Ouyang, X., et al. (2007). Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proc. Natl. Acad. Sci. USA 104, 13798–13803.10.1073/pnas.0702553104Search in Google Scholar

Tang, S.C., Lathia, J.D., Selvaraj, P.K., Jo, D.G., Mughal, M.R., Cheng, A., Siler, D.A., Markesbery, W.R., Arumugam, T.V., and Mattson, M.P. (2008). Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal. Exp. Neurol. 213, 114–121.10.1016/j.expneurol.2008.05.014Search in Google Scholar

Tasaki, K., Ruetzler, C.A., Ohtsuki, T., Martin, D., Nawashiro, H., and Hallenbeck, J.M. (1997). Lipopolysaccharide pre-treatment induces resistance against subsequent focal cerebral ischemic damage in spontaneously hypertensive rats. Brain Res. 748, 267–270.10.1016/S0006-8993(96)01383-2Search in Google Scholar

Taylor, K.R., Yamasaki, K., Radek, K.A., Di Nardo, A., Goodarzi, H., Golenbock, D., Beutler, B., and Gallo, R.L. (2007). Recognition of hyaluronan released in sterile injury involves a unique receptor complex dependent on Toll-like receptor 4, CD44, and MD-2. J. Biol. Chem. 282, 18265–18275.10.1074/jbc.M606352200Search in Google Scholar PubMed

Termeer, C., Benedix, F., Sleeman, J., Fieber, C., Voith, U., Ahrens, T., Miyake, K., Freudenberg, M., Galanos, C., and Simon, J.C. (2002). Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4. J. Exp. Med. 195, 99–111.10.1084/jem.20001858Search in Google Scholar PubMed PubMed Central

Vabulas, R.M., Ahmad-Nejad, P., da Costa, C., Miethke, T., Kirschning, C.J., Häcker, H., and Wagner, H. (2001). Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J. Biol. Chem. 276, 31332–31339.10.1074/jbc.M103217200Search in Google Scholar PubMed

Vabulas, R.M., Ahmad-Nejad, P., Ghose, S., Kirschning, C.J., Issels, R.D., and Wagner, H. (2002a). HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J. Biol. Chem. 277, 15107–15112.10.1074/jbc.M111204200Search in Google Scholar PubMed

Vabulas, R.M., Braedel, S., Hilf, N., Singh-Jasuja, H., Herter, S., Ahmad-Nejad, P., Kirschning, C.J., Da Costa, C., Rammensee, H.G., Wagner, H., et al. (2002b). The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway. J. Biol. Chem. 277, 20847–20853.10.1074/jbc.M200425200Search in Google Scholar PubMed

Vollmer, J., Tluk, S., Schmitz, C., Hamm, S., Jurk, M., Forsbach, A., Akira, S., Kelly, K.M., Reeves, W.H., Bauer, S., et al. (2005). Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8. J. Exp. Med. 202, 1575–1585.10.1084/jem.20051696Search in Google Scholar PubMed PubMed Central

Waldner, H. (2009). The role of innate immune responses in autoimmune disease development. Autoimmun. Rev. 8, 400–404.10.1016/j.autrev.2008.12.019Search in Google Scholar PubMed

Wysocka, M., Robertson, S., Riemann, H., Caamano, J., Hunter, C., Mackiewicz, A., Montaner, L.J., Trinchieri, G., and Karp, C.L. (2001). IL-12 suppression during experimental endotoxin tolerance: dendritic cell loss and macrophage hyporesponsiveness. J. Immunol. 166, 7504–7513.10.4049/jimmunol.166.12.7504Search in Google Scholar PubMed

Yamamoto, M., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Sanjo, H., Takeuchi, O., Sugiyama, M., Okabe, M., Takeda. K., et al. (2003). Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301, 640–643.10.1126/science.1087262Search in Google Scholar PubMed

Yang, Q.W., Li, J.C., Lu, F.L., Wen, A.Q., Xiang, J., Zhang, L.L., Huang, Z.Y., and Wang, J.Z. (2008). Upregulated expression of toll-like receptor 4 in monocytes correlates with severity of acute cerebral infarction. J. Cereb. Blood Flow Metab. 28, 1588–1596.10.1038/jcbfm.2008.50Search in Google Scholar PubMed

Yang, Q.W., Lu, F.L., Zhou, Y., Wang, L., Zhong, Q., Lin, S., Xiang, J., Li, J.C., Fang, C.Q., and Wang, J.Z. (2011). HMBG1 mediates ischemia-reperfusion injury by TRIF-adaptor independent Toll-like receptor 4 signaling. J. Cereb. Blood Flow Metab. 31, 593–605.10.1038/jcbfm.2010.129Search in Google Scholar PubMed PubMed Central

Yarovinsky, F., Zhang, D., Andersen, J.F., Bannenberg, G.L., Serhan, C.N., Hayden, M.S., Hieny, S., Sutterwala, F.S., Flavell, R.A., Ghosh, S., et al. (2005). TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 308, 1626–1629.10.1126/science.1109893Search in Google Scholar PubMed

Yeo, S.J., Yoon, J.G., Hong, S.C., and Yi, A.K. (2003). CpG DNA induces self and cross-hyporesponsiveness of RAW264.7 cells in response to CpG DNA and lipopolysaccharide: alterations in IL-1 receptor-associated kinase expression. J. Immunol. 170, 1052–1061.10.4049/jimmunol.170.2.1052Search in Google Scholar PubMed

Ziegler, G., Harhausen, D., Schepers, C., Hoffmann, O., Röhr, C., Prinz, V., König, J., Lehrach, H., Nietfeld, W., and Trendelenburg, G. (2007). TLR2 has a detrimental role in mouse transient focal cerebral ischemia. Biochem. Biophys. Res. Commun. 359, 574–579.10.1016/j.bbrc.2007.05.157Search in Google Scholar PubMed

Ziegler, G., Freyer, D., Harhausen, D., Khojasteh, U., Nietfeld, W., and Trendelenburg, G. (2011). Blocking TLR2 in vivo protects against accumulation of inflammatory cells and neuronal injury in experimental stroke. J. Cereb. Blood Flow Metab. 31, 757–766.10.1038/jcbfm.2010.161Search in Google Scholar PubMed PubMed Central

Zierath, D., Thullbery, M., Hadwin, J., Gee, J.M., Savos, A., Kalil, A., and Becker, K.J. (2010). CNS immune responses following experimental stroke. Neurocrit. Care 12, 274–284.10.1007/s12028-009-9270-4Search in Google Scholar PubMed PubMed Central