title: Toll-like receptors in brain abscess.
abstract: Brain abscesses arise from a localized parenchymal infection, typically elicited by pyogenic bacteria such as Staphylococcus aureus. Despite improvements in detection and treatment strategies, brain abscesses continue to occur, with an increased prevalence in developing countries and immune-compromised patients. Adding to the seriousness of these infections is the recent emergence of antibiotic-resistant strains of bacteria, which are becoming more commonly associated with brain abscesses. Recent studies using a mouse experimental brain abscess model have revealed a complex role for Toll-like receptors (TLRs) in disease pathogenesis. Interestingly, TLR2 has limited impact on the innate immune response during the acute stage of brain abscess formation induced by S. aureus but influences adaptive immunity. In contrast, mice deficient in MyD88, a central adapter molecule for the majority of TLRs in addition to the IL-1R and IL-18R, demonstrate severe defects in innate immunity coupled with exaggerated tissue destruction. It is envisioned that understanding the roles for TLRs in both resident CNS glia as well as infiltrating immune cells will provide insights into how the immune response to bacterial infection can be tailored to achieve effective pathogen destruction without inducing excessive bystander damage of surrounding noninfected brain parenchyma. A discussion of recent findings in this field is presented along with outstanding questions and the concept of a pathogen-necrosis-autoantigen triad for the amplification of TLR signaling is introduced.
authors.affiliation: Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Nilufer
authors.initials: N
authors.lastname: Esen
authors.forename: Tammy
authors.initials: T
authors.lastname: Kielian
mesh_terms: D000818:Animals; D001922:Brain Abscess / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*
chemical_list: D051195:Toll-Like Receptor 2
references.citation: Stroke. 1995 Apr;26(4):696-8
references.pmid: 7709419
references.citation: Neuro Endocrinol Lett. 2007 Jun;28 Suppl 2:5-6
references.pmid: 17558364
references.citation: J Biol Chem. 2004 Jan 23;279(4):2559-67
references.pmid: 14600152
references.citation: J Biol Chem. 2003 Oct 24;278(43):41702-8
references.pmid: 12871942
references.citation: J Neuroimmunol. 1997 Jan;72(1):83-93
references.pmid: 9003248
references.citation: J Immunol. 2000 Nov 15;165(10):5814-21
references.pmid: 11067941
references.citation: J Neuroinflammation. 2007 Mar 20;4:10
references.pmid: 17374157
references.citation: Nat Rev Immunol. 2005 Jan;5(1):69-81
references.pmid: 15630430
references.citation: Nat Rev Immunol. 2008 May;8(5):337-48
references.pmid: 18408735
references.citation: J Immunol. 2002 Nov 15;169(10):5897-903
references.pmid: 12421973
references.citation: J Immunol. 2008 Sep 15;181(6):3841-9
references.pmid: 18768838
references.citation: J Immunol. 1998 May 15;160(10):4671-80
references.pmid: 9590212
references.citation: Am J Pathol. 2008 Jan;172(1):132-45
references.pmid: 18165267
references.citation: J Neuroimmunol. 2002 Sep;130(1-2):22-31
references.pmid: 12225885
references.citation: Nat Immunol. 2004 Oct;5(10):971-4
references.pmid: 15454919
references.citation: Clin Microbiol Rev. 2003 Jul;16(3):415-29
references.pmid: 12857775
references.citation: Brain Behav Immun. 2003 Feb;17(1):13-9
references.pmid: 12615045
references.citation: J Neuropathol Exp Neurol. 2002 Nov;61(11):1013-21
references.pmid: 12430718
references.citation: J Immunol. 2006 Jun 1;176(11):6802-11
references.pmid: 16709840
references.citation: Neurosci Lett. 1995 Apr 14;189(2):97-100
references.pmid: 7609927
references.citation: Trends Immunol. 2007 Mar;28(3):138-45
references.pmid: 17276138
references.citation: Glia. 2005 Feb;49(3):360-74
references.pmid: 15538753
references.citation: Glia. 2005 Mar;49(4):567-76
references.pmid: 15593098
references.citation: J Coll Physicians Surg Pak. 2004 Jul;14(7):407-10
references.pmid: 15279742
references.citation: Am J Pathol. 1992 Dec;141(6):1299-307
references.pmid: 1281616
references.citation: J Immunol. 2002 Oct 1;169(7):3970-7
references.pmid: 12244198
references.citation: J Exp Med. 2002 Jun 3;195(11):1471-8
references.pmid: 12045245
references.citation: Curr Opin Immunol. 2002 Feb;14(1):123-8
references.pmid: 11790542
references.citation: Microbes Infect. 2004 Dec;6(15):1368-73
references.pmid: 15596122
references.citation: Neuroepidemiology. 1991;10(3):122-31
references.pmid: 1922645
references.citation: J Immunol. 2003 Feb 15;170(4):1958-63
references.pmid: 12574364
references.citation: Annu Rev Neurosci. 1999;22:219-40
references.pmid: 10202538
references.citation: Transpl Infect Dis. 2007 Jun;9(2):142-7
references.pmid: 17462001
references.citation: Clin Transplant. 2002 Dec;16(6):419-24
references.pmid: 12437621
references.citation: Clin Microbiol Infect. 2003 Aug;9(8):803-9
references.pmid: 14616700
references.citation: Curr Opin Immunol. 2003 Aug;15(4):408-15
references.pmid: 12900272
references.citation: J Immunol. 2001 Feb 15;166(4):2260-9
references.pmid: 11160280
references.citation: J Neurochem. 2004 Feb;88(3):746-58
references.pmid: 14720224
references.citation: J Immunol. 2005 Oct 1;175(7):4320-30
references.pmid: 16177072
references.citation: J Immunol. 2000 Nov 15;165(10):5392-6
references.pmid: 11067888
references.citation: Semin Neurol. 2000;20(3):353-60
references.pmid: 11051299
references.citation: Neurol Clin. 1986 Feb;4(1):91-114
references.pmid: 3523205
references.citation: Scand J Infect Dis. 1988;20(1):1-9
references.pmid: 3363298
references.citation: Cell Mol Life Sci. 2003 Sep;60(9):1793-804
references.pmid: 14523544
references.citation: Am J Pathol. 2000 Aug;157(2):647-58
references.pmid: 10934167
references.citation: Nat Rev Neurosci. 2007 Jan;8(1):57-69
references.pmid: 17180163
references.citation: J Neurosurg. 1979 Nov;51(5):685-90
references.pmid: 387920
references.citation: J Neuroinflammation. 2004 Aug 17;1(1):16
references.pmid: 15315708
references.citation: Eur J Clin Microbiol Infect Dis. 2007 Jan;26(1):1-11
references.pmid: 17180609
references.citation: Adv Intern Med. 1998;43:403-47
references.pmid: 9506189
references.citation: J Neurovirol. 2002 Dec;8(6):529-38
references.pmid: 12476347
references.citation: J Immunol. 1994 Mar 15;152(6):2720-8
references.pmid: 8144879
references.citation: J Microbiol Immunol Infect. 2003 Jun;36(2):129-36
references.pmid: 12886965
references.citation: J Immunol. 2001 Apr 1;166(7):4634-43
references.pmid: 11254722
references.citation: J Immunol. 2004 Sep 15;173(6):3916-24
references.pmid: 15356140
references.citation: J Neuropathol Exp Neurol. 2004 Apr;63(4):381-96
references.pmid: 15099027
references.citation: Adv Exp Med Biol. 2005;560:11-8
references.pmid: 15932016
references.citation: J Neurochem. 2004 Sep;90(5):1163-72
references.pmid: 15312171
references.citation: J Immunol. 2003 Jan 1;170(1):438-44
references.pmid: 12496429
references.citation: Turk Neurosurg. 2007;17(1):48-54
references.pmid: 17918680
references.citation: J Infect Dis. 2002 Sep 15;186(6):798-806
references.pmid: 12198614
references.citation: Mycoses. 2008 Jul;51(4):275-90
references.pmid: 18331448
references.citation: J Mol Med (Berl). 1997 Mar;75(3):165-73
references.pmid: 9106073
references.citation: Infect Immun. 2005 Aug;73(8):5212-6
references.pmid: 16041042
references.citation: J Infect. 2006 Oct;53(4):221-7
references.pmid: 16436297
references.citation: J Biol Chem. 2003 Mar 14;278(11):8869-72
references.pmid: 12527755
references.citation: Am J Pathol. 1999 Nov;155(5):1599-611
references.pmid: 10550317
references.citation: Clin Infect Dis. 1997 Oct;25(4):763-79; quiz 780-1
references.pmid: 9356788
references.citation: J Neuroimmunol. 2005 Dec 30;170(1-2):93-104
references.pmid: 16229899
references.citation: J Neuroimmunol. 2004 Jun;151(1-2):24-32
references.pmid: 15145600
references.citation: J Neurosurg. 1981 Oct;55(4):590-603
references.pmid: 6168748
references.citation: J Immunol. 2007 Apr 1;178(7):4528-37
references.pmid: 17372011
references.citation: Int J STD AIDS. 1997 Jul;8(7):459-60
references.pmid: 9228595
references.citation: J Immunol. 2002 Jul 1;169(1):10-4
references.pmid: 12077222
references.citation: Neuro Endocrinol Lett. 2007 Jun;28 Suppl 2:25-6
references.pmid: 17558372
references.citation: South Med J. 2008 Jun;101(6):618-25
references.pmid: 18475224
references.citation: J Neurochem. 2007 Nov;103(4):1461-71
references.pmid: 17961202
references.citation: Nat Rev Microbiol. 2003 Nov;1(2):151-7
references.pmid: 15035044
references.citation: Ann Clin Microbiol Antimicrob. 2004 Mar 25;3:3
references.pmid: 15043754
references.citation: J Leukoc Biol. 2004 Jul;76(1):135-44
references.pmid: 15107456
references.citation: Glia. 2001 Nov;36(2):180-90
references.pmid: 11596126
references.citation: J Immunol. 2002 May 15;168(10):4854-63
references.pmid: 11994434
references.citation: Infect Immun. 2001 Nov;69(11):6902-11
references.pmid: 11598065
references.citation: J Exp Med. 2001 Aug 20;194(4):519-27
references.pmid: 11514607
references.citation: Glia. 2002 Nov;40(2):195-205
references.pmid: 12379907
references.citation: J Neuropathol Exp Neurol. 2004 Jun;63(6):631-40
references.pmid: 15217091
references.citation: Infect Immun. 2005 Nov;73(11):7428-35
references.pmid: 16239543
references.citation: J Neurol Neurosurg Psychiatry. 1978 Nov;41(11):1043-7
references.pmid: 712373
references.citation: J Biol Chem. 2003 Feb 21;278(8):5509-12
references.pmid: 12514169
references.citation: J Neuroimmunol. 2002 Sep;130(1-2):86-99
references.pmid: 12225891
references.citation: Glia. 2003 Sep;43(3):281-91
references.pmid: 12898707
references.citation: J Immunol. 2001 Nov 15;167(10):6015-20
references.pmid: 11698482
references.citation: Indian J Pediatr. 2000 Mar;67(3  Suppl):S15-9
references.pmid: 11129914
references.citation: Glia. 2001 Nov;36(2):165-79
references.pmid: 11596125
references.citation: Scand J Infect Dis. 2000;32(4):423-4
references.pmid: 10959655