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Department of Microbiology-Immunology and Interdepartmental Immunobiology Program, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611
Microglia are the resident macrophage-like population in the CNS. Microglia remain quiescent until injury or infection activates the cells to perform effector inflammatory and APC functions. Our previous studies have shown that microglia infected with a neurotropic strain of Theiler’s murine encephalomyelitis virus secreted innate immune cytokines and up-regulated costimulatory molecules and MHC class II, enabling the cells to present viral and myelin Ags to CD4+ T cells. Recently, TLRs have been shown to recognize pathogen-associated molecular patterns and initiate innate immune responses upon interaction with infectious agents. We examined TLR expression on brain microglia and their functional responses upon stimulation with various TLR agonists. We report that mouse microglia express mRNA for all of the recently identified TLRs, TLR1–9, used for recognition of bacterial and viral molecular patterns. Furthermore, stimulation of quiescent microglia with various TLR agonists, including LPS (TLR4), peptidoglycan (TLR2), polyinosinic-polycytidylic acid (TLR3), CpG DNA (TLR9), and infection with viable Theiler’s murine encephalomyelitis virus, activated the cells to up-regulate unique patterns of innate and effector immune cytokines and chemokines at the mRNA and protein levels. In addition, TLR stimulation activated up-regulation of MHC class II and costimulatory molecules, enabling the microglia to efficiently present myelin Ags to CD4+ T cells. Thus, microglia appear to be a unique and important component of both the innate and adaptive immune response, providing the CNS with a means to rapidly and efficiently respond to a wide variety of pathogens.
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H. Zhou, B. M. Lapointe, S. R. Clark, L. Zbytnuik, and P. Kubes A Requirement for Microglial TLR4 in Leukocyte Recruitment into Brain in Response to Lipopolysaccharide J. Immunol., December 1, 2006; 177(11): 8103 - 8110. [Abstract] [Full Text] [PDF]
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A. Riccioli, D. Starace, R. Galli, A. Fuso, S. Scarpa, F. Palombi, P. De Cesaris, E. Ziparo, and A. Filippini Sertoli Cells Initiate Testicular Innate Immune Responses through TLR Activation J. Immunol., November 15, 2006; 177(10): 7122 - 7130. [Abstract] [Full Text] [PDF]
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K. Tahara, H.-D. Kim, J.-J. Jin, J. A. Maxwell, L. Li, and K.-i. Fukuchi Role of toll-like receptor signalling in A{beta} uptake and clearance Brain, November 1, 2006; 129(11): 3006 - 3019. [Abstract] [Full Text] [PDF]
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M. A. Rivieccio, H.-S. Suh, Y. Zhao, M.-L. Zhao, K. C. Chin, S. C. Lee, and C. F. Brosnan TLR3 Ligation Activates an Antiviral Response in Human Fetal Astrocytes: A Role for Viperin/cig5 J. Immunol., October 1, 2006; 177(7): 4735 - 4741. [Abstract] [Full Text] [PDF]
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E. H. Tran, Y.-T. Azuma, M. Chen, C. Weston, R. J. Davis, and R. A. Flavell Inactivation of JNK1 enhances innate IL-10 production and dampens autoimmune inflammation in the brain PNAS, September 5, 2006; 103(36): 13451 - 13456. [Abstract] [Full Text] [PDF]
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I. Herrmann, M. Kellert, H. Schmidt, A. Mildner, U. K. Hanisch, W. Bruck, M. Prinz, and R. Nau Streptococcus pneumoniae Infection Aggravates Experimental Autoimmune Encephalomyelitis via Toll-Like Receptor 2. Infect. Immun., August 1, 2006; 74(8): 4841 - 4848. [Abstract] [Full Text] [PDF]
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N. Esen and T. Kielian Central Role for MyD88 in the Responses of Microglia to Pathogen-Associated Molecular Patterns. J. Immunol., June 1, 2006; 176(11): 6802 - 6811. [Abstract] [Full Text] [PDF]
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I. Jou, J. H. Lee, S. Y. Park, H. J. Yoon, E.-H. Joe, and E. J. Park Gangliosides Trigger Inflammatory Responses via TLR4 in Brain Glia Am. J. Pathol., May 1, 2006; 168(5): 1619 - 1630. [Abstract] [Full Text] [PDF]
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T. Town, D. Jeng, L. Alexopoulou, J. Tan, and R. A. Flavell Microglia Recognize Double-Stranded RNA via TLR3 J. Immunol., March 15, 2006; 176(6): 3804 - 3812. [Abstract] [Full Text] [PDF]
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K. Chen, P. Iribarren, J. Hu, J. Chen, W. Gong, E. H. Cho, S. Lockett, N. M. Dunlop, and J. M. Wang Activation of Toll-like Receptor 2 on Microglia Promotes Cell Uptake of Alzheimer Disease-associated Amyloid beta Peptide J. Biol. Chem., February 10, 2006; 281(6): 3651 - 3659. [Abstract] [Full Text] [PDF]
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Z. Guo, S. Garg, K. M. Hill, L. Jayashankar, M. R. Mooney, M. Hoelscher, J. M. Katz, J. M. Boss, and S. Sambhara A Distal Regulatory Region Is Required for Constitutive and IFN-{beta}-Induced Expression of Murine TLR9 Gene J. Immunol., December 1, 2005; 175(11): 7407 - 7418. [Abstract] [Full Text] [PDF]
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R. N. Aravalli, S. Hu, T. N. Rowen, J. M. Palmquist, and J. R. Lokensgard Cutting Edge: TLR2-Mediated Proinflammatory Cytokine and Chemokine Production by Microglial Cells in Response to Herpes Simplex Virus J. Immunol., October 1, 2005; 175(7): 4189 - 4193. [Abstract] [Full Text] [PDF]
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C. S. Jack, N. Arbour, J. Manusow, V. Montgrain, M. Blain, E. McCrea, A. Shapiro, and J. P. Antel TLR Signaling Tailors Innate Immune Responses in Human Microglia and Astrocytes J. Immunol., October 1, 2005; 175(7): 4320 - 4330. [Abstract] [Full Text] [PDF]
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K. Nakamichi, M. Saiki, M. Sawada, M. Takayama-Ito, Y. Yamamuro, K. Morimoto, and I. Kurane Rabies Virus-Induced Activation of Mitogen-Activated Protein Kinase and NF-{kappa}B Signaling Pathways Regulates Expression of CXC and CC Chemokine Ligands in Microglia J. Virol., September 15, 2005; 79(18): 11801 - 11812. [Abstract] [Full Text] [PDF]
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J. L. Croxford, J. K. Olson, H. A. Anger, and S. D. Miller Initiation and Exacerbation of Autoimmune Demyelination of the Central Nervous System via Virus-Induced Molecular Mimicry: Implications for the Pathogenesis of Multiple Sclerosis J. Virol., July 1, 2005; 79(13): 8581 - 8590. [Abstract] [Full Text] [PDF]
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S.-K. Kim and J. C. Boothroyd Stage-Specific Expression of Surface Antigens by Toxoplasma gondii as a Mechanism to Facilitate Parasite Persistence J. Immunol., June 15, 2005; 174(12): 8038 - 8048. [Abstract] [Full Text] [PDF]
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D. Y. Jung, H. Lee, B.-Y. Jung, J. Ock, M.-S. Lee, W.-H. Lee, and K. Suk TLR4, but Not TLR2, Signals Autoregulatory Apoptosis of Cultured Microglia: A Critical Role of IFN-{beta} as a Decision Maker J. Immunol., May 15, 2005; 174(10): 6467 - 6476. [Abstract] [Full Text] [PDF]
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