Abstract
Microglia are the resident macrophage population in the central nervous system (CNS) parenchyma and, as such, are poised to provide a first line of defense against invading pathogens. Microglia are endowed with a vast repertoire of pattern recognition receptors that include such family members as Toll-like receptors and phagocytic receptors, which collectively function to sense and eliminate microbes invading the CNS parenchyma. In addition, microglial activation elicits a broad range of pro-inflammatory cytokines and chemokines that are involved in the recruitment and subsequent activation of peripheral immune cells infiltrating the infected CNS. Studies from several laboratories have demonstrated the ability of microglia to sense and respond to a wide variety of pathogens capable of colonizing the CNS including bacterial, viral, and fungal species. This review will highlight the role of microglia in microbial recognition and the resultant antipathogen response that ensues in an attempt to clear these infections. Implications as to whether microglial activation is uniformly beneficial to the CNS or in some circumstances may exacerbate pathology will also be discussed.
Similar content being viewed by others
References
Adachi O, Kawai T, Takeda K, Matsumoto M, Tsutsui H, Sakagami M, Nakanishi K, Akira S (1998) Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 9(1):143–150
Aguirre K, Miller S (2002) MHC class II-positive perivascular microglial cells mediate resistance to Cryptococcus neoformans brain infection. Glia 39(2):184–188
Akira S (2006) TLR signaling. Curr Top Microbiol Immunol 311:1–16
Aloisi F (2001) Immune function of microglia. Glia 36(2):165–179
Aravalli RN, Hu S, Woods JP, Lokensgard JR (2008) Histoplasma capsulatum yeast phase-specific protein Yps3p induces Toll-like receptor 2 signaling. J Neuroinflammation 5:30
Baldwin AC, Kielian T (2004) Persistent immune activation associated with a mouse model of Staphylococcus aureus-induced experimental brain abscess. J Neuroimmunol 151(1–2):24–32
Bernardino AL, Myers TA, Alvarez X, Hasegawa A, Philipp MT (2008) Toll-like receptors: insights into their possible role in the pathogenesis of lyme neuroborreliosis. Infect Immun 76(10):4385–4395
Bernardino AL, Kaushal D, Philipp MT (2009) The antibiotics doxycycline and minocycline inhibit the inflammatory responses to the lyme disease spirochete Borrelia burgdorferi. J Infect Dis 199(9):1379–1388
Blasi E, Barluzzi R, Mazzolla R, Tancini B, Saleppico S, Puliti M, Pitzurra L, Bistoni F (1995) Role of nitric oxide and melanogenesis in the accomplishment of anticryptococcal activity by the BV-2 microglial cell line. J Neuroimmunol 58(1):111–116
Brandenburg LO, Varoga D, Nicolaeva N, Leib SL, Wilms H, Podschun R, Wruck CJ, Schroder JM, Pufe T, Lucius R (2008) Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis. J Neuropathol Exp Neurol 67(11):1041–1054
Braun JS, Novak R, Murray PJ, Eischen CM, Susin SA, Kroemer G, Halle A, Weber JR, Tuomanen EI, Cleveland JL (2001) Apoptosis-inducing factor mediates microglial and neuronal apoptosis caused by pneumococcus. J Infect Dis 184(10):1300–1309
Braun JS, Sublett JE, Freyer D, Mitchell TJ, Cleveland JL, Tuomanen EI, Weber JR (2002) Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis during meningitis. J Clin Invest 109(1):19–27
Burns K, Martinon F, Esslinger C, Pahl H, Schneider P, Bodmer JL, Di Marco F, French L, Tschopp J (1998) MyD88, an adapter protein involved in interleukin-1 signaling. J Biol Chem 273(20):12203–12209
Carson MJ, Reilly CR, Sutcliffe JG, Lo D (1998) Mature microglia resemble immature antigen-presenting cells. Glia 22(1):72–85
Cassiani-Ingoni R, Cabral ES, Lunemann JD, Garza Z, Magnus T, Gelderblom H, Munson PJ, Marques A, Martin R (2006) Borrelia burgdorferi induces TLR1 and TLR2 in human microglia and peripheral blood monocytes but differentially regulates HLA-class II expression. J Neuropathol Exp Neurol 65(6):540–548
Chao CC, Anderson WR, Hu S, Gekker G, Martella A, Peterson PK (1993) Activated microglia inhibit multiplication of Toxoplasma gondii via a nitric oxide mechanism. Clin Immunol Immunopathol 67(2):178–183
Chao CC, Gekker G, Hu S, Peterson PK (1994) Human microglial cell defense against Toxoplasma gondii. The role of cytokines. J Immunol 152(3):1246–1252
Coban C, Ishii KJ, Uematsu S, Arisue N, Sato S, Yamamoto M, Kawai T, Takeuchi O, Hisaeda H, Horii T et al (2007) Pathological role of Toll-like receptor signaling in cerebral malaria. Int Immunol 19(1):67–79
Colton C, Wilt S, Gilbert D, Chernyshev O, Snell J, Dubois-Dalcq M (1996) Species differences in the generation of reactive oxygen species by microglia. Mol Chem Neuropathol 28(1–3):15–20
Das Sarma J, Ciric B, Marek R, Sadhukhan S, Caruso ML, Shafagh J, Fitzgerald DC, Shindler KS, Rostami AM (2009) Functional interleukin-17 receptor A is expressed in central nervous system glia and upregulated in experimental autoimmune encephalomyelitis. J Neuroinflammation 6(1):14
Deckert M, Sedgwick JD, Fischer E, Schluter D (2006) Regulation of microglial cell responses in murine Toxoplasma encephalitis by CD200/CD200 receptor interaction. Acta Neuropathol 111(6):548–558
Deckert-Schluter M, Buck C, Weiner D, Kaefer N, Rang A, Hof H, Wiestler OD, Schluter D (1997) Interleukin-10 downregulates the intracerebral immune response in chronic Toxoplasma encephalitis. J Neuroimmunol 76(1–2):167–176
Deininger MH, Kremsner PG, Meyermann R, Schluesener H (2002) Macrophages/microglial cells in patients with cerebral malaria. Eur Cytokine Netw 13(2):173–185
Djukic M, Mildner A, Schmidt H, Czesnik D, Bruck W, Priller J, Nau R, Prinz M (2006) Circulating monocytes engraft in the brain, differentiate into microglia and contribute to the pathology following meningitis in mice. Brain 129(Pt 9):2394–2403
Dobbie M, Crawley J, Waruiru C, Marsh K, Surtees R (2000) Cerebrospinal fluid studies in children with cerebral malaria: an excitotoxic mechanism? Am J Trop Med Hyg 62(2):284–290
Engwerda C, Belnoue E, Gruner AC, Renia L (2005) Experimental models of cerebral malaria. Curr Top Microbiol Immunol 297:103–143
Esen N, Kielian T (2006) Central role for MyD88 in the responses of microglia to pathogen-associated molecular patterns. J Immunol 176(11):6802–6811
Esen N, Kielian T (2007) Effects of low dose GM-CSF on microglial inflammatory profiles to diverse pathogen-associated molecular patterns (PAMPs). J Neuroinflammation 4:10
Fischer HG, Reichmann G (2001) Brain dendritic cells and macrophages/microglia in central nervous system inflammation. J Immunol 166(4):2717–2726
Fischer HG, Bielinsky AK, Nitzgen B, Daubener W, Hadding U (1993) Functional dichotomy of mouse microglia developed in vitro: differential effects of macrophage and granulocyte/macrophage colony-stimulating factor on cytokine secretion and antitoxoplasmic activity. J Neuroimmunol 45(1–2):193–201
Fischer HG, Nitzgen B, Reichmann G, Gross U, Hadding U (1997) Host cells of Toxoplasma gondii encystation in infected primary culture from mouse brain. Parasitol Res 83(7):637–641
Ford AL, Goodsall AL, Hickey WF, Sedgwick JD (1995) Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. J Immunol 154(9):4309–4321
Freund YR, Zaveri NT, Javitz HS (2001) In vitro investigation of host resistance to Toxoplasma gondii infection in microglia of BALB/c and CBA/Ca mice. Infect Immun 69(2):765–772
Galiza EP, Heath PT (2009) Improving the outcome of neonatal meningitis. Curr Opin Infect Dis 22(3):229–234
Garcao P, Oliveira CR, Agostinho P (2006) Comparative study of microglia activation induced by amyloid-beta and prion peptides: role in neurodegeneration. J Neurosci Res 84(1):182–193
Garg S, Nichols JR, Esen N, Liu S, Phulwani NK, Syed MMd, Wood WH, Zhang Y, Becker KG, Aldrich A, Kielian T (2009) MyD88 expression by CNS-resident cells is pivotal for eliciting protective immunity in brain abscesses. ASN Neuro. doi:10.1042/AN20090004
Goos M, Lange P, Hanisch UK, Prinz M, Scheffel J, Bergmann R, Ebert S, Nau R (2007) Fibronectin is elevated in the cerebrospinal fluid of patients suffering from bacterial meningitis and enhances inflammation caused by bacterial products in primary mouse microglial cell cultures. J Neurochem 102(6):2049–2060
Griffith JW, O'Connor C, Bernard K, Town T, Goldstein DR, Bucala R (2007) Toll-like receptor modulation of murine cerebral malaria is dependent on the genetic background of the host. J Infect Dis 196(10):1553–1564
Gurley C, Nichols J, Liu S, Phulwani NK, Esen N, Kielian T (2008) Microglia and astrocyte activation by Toll-like receptor ligands: modulation by PPAR-gamma agonists. PPAR Res 2008:453120
Hanisch UK (2002) Microglia as a source and target of cytokines. Glia 40(2):140–155
Hanisch UK, Prinz M, Angstwurm K, Hausler KG, Kann O, Kettenmann H, Weber JR (2001) The protein tyrosine kinase inhibitor AG126 prevents the massive microglial cytokine induction by pneumococcal cell walls. Eur J Immunol 31(7):2104–2115
Hengge UR, Tannapfel A, Tyring SK, Erbel R, Arendt G, Ruzicka T (2003) Lyme borreliosis. Lancet Infect Dis 3(8):489–500
Hill JO, Aguirre KM (1994) CD4+ T cell-dependent acquired state of immunity that protects the brain against Cryptococcus neoformans. J Immunol 152(5):2344–2350
Hunt NH, Golenser J, Chan-Ling T, Parekh S, Rae C, Potter S, Medana IM, Miu J, Ball HJ (2006) Immunopathogenesis of cerebral malaria. Int J Parasitol 36(5):569–582
Husemann J, Loike JD, Anankov R, Febbraio M, Silverstein SC (2002) Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system. Glia 40(2):195–205
Idro R, Jenkins NE, Newton CR (2005) Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol 4(12):827–840
Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y, Fujikado N, Tanahashi Y, Akitsu A, Kotaki H et al (2009) Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30(1):108–119
Jones ME, Draghi DC, Karlowsky JA, Sahm DF, Bradley JS (2004) Prevalence of antimicrobial resistance in bacteria isolated from central nervous system specimens as reported by U.S. hospital laboratories from 2000 to 2002. Ann Clin Microbiol Antimicrob 3:3
Kawanokuchi J, Shimizu K, Nitta A, Yamada K, Mizuno T, Takeuchi H, Suzumura A (2008) Production and functions of IL-17 in microglia. J Neuroimmunol 194(1–2):54–61
Kielian T (2004) Immunopathogenesis of brain abscess. J Neuroinflammation 1(1):16
Kielian T (2006) Toll-like receptors in central nervous system glial inflammation and homeostasis. J Neurosci Res 83(5):711–730
Kielian T, Barry B, Hickey WF (2001) CXC chemokine receptor-2 ligands are required for neutrophil-mediated host defense in experimental brain abscesses. J Immunol 166(7):4634–4643
Kielian T, Mayes P, Kielian M (2002) Characterization of microglial responses to Staphylococcus aureus: effects on cytokine, costimulatory molecule, and Toll-like receptor expression. J Neuroimmunol 130(1–2):86–99
Kielian T, Bearden ED, Baldwin AC, Esen N (2004) IL-1 and TNF-alpha play a pivotal role in the host immune response in a mouse model of Staphylococcus aureus-induced experimental brain abscess. J Neuropathol Exp Neurol 63(4):381–396
Kielian T, Esen N, Bearden ED (2005) Toll-like receptor 2 (TLR2) is pivotal for recognition of S. aureus peptidoglycan but not intact bacteria by microglia. Glia 49(4):567–576
Kielian T, Phulwani NK, Esen N, Syed MM, Haney AC, McCastlain K, Johnson J (2007) MyD88-dependent signals are essential for the host immune response in experimental brain abscess. J Immunol 178(7):4528–4537
Kim YS, Tauber MG (1996) Neurotoxicity of glia activated by gram-positive bacterial products depends on nitric oxide production. Infect Immun 64(8):3148–3153
Kim K, Weiss LM (2008) Toxoplasma: the next 100 years. Microbes Infect 10(9):978–984
Kleinert H, Pautz A, Linker K, Schwarz PM (2004) Regulation of the expression of inducible nitric oxide synthase. Eur J Pharmacol 500(1–3):255–266
Kleinschek MA, Muller U, Brodie SJ, Stenzel W, Kohler G, Blumenschein WM, Straubinger RK, McClanahan T, Kastelein RA, Alber G (2006) IL-23 enhances the inflammatory cell response in Cryptococcus neoformans infection and induces a cytokine pattern distinct from IL-12. J Immunol 176(2):1098–1106
Koedel U, Scheld WM, Pfister HW (2002) Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis 2(12):721–736
Larsen PH, Holm TH, Owens T (2007) Toll-like receptors in brain development and homeostasis. Sci STKE 2007(402):pe47
Lee SC, Kress Y, Dickson DW, Casadevall A (1995) Human microglia mediate anti-Cryptococcus neoformans activity in the presence of specific antibody. J Neuroimmunol 62(1):43–52
Lehnardt S, Wennekamp J, Freyer D, Liedtke C, Krueger C, Nitsch R, Bechmann I, Weber JR, Henneke P (2007) TLR2 and caspase-8 are essential for group B Streptococcus-induced apoptosis in microglia. J Immunol 179(9):6134–6143
Lepenies B, Cramer JP, Burchard GD, Wagner H, Kirschning CJ, Jacobs T (2008) Induction of experimental cerebral malaria is independent of TLR2/4/9. Med Microbiol Immunol 197(1):39–44
Lipovsky MM, Gekker G, Anderson WR, Molitor TW, Peterson PK, Hoepelman AI (1997) Phagocytosis of nonopsonized Cryptococcus neoformans by swine microglia involves CD14 receptors. Clin Immunol Immunopathol 84(2):208–211
Lipovsky MM, Juliana AE, Gekker G, Hu S, Hoepelman AI, Peterson PK (1998) Effect of cytokines on anticryptococcal activity of human microglial cells. Clin Diagn Lab Immunol 5(3):410–411
Lu CH, Chang WN, Lui CC (2006) Strategies for the management of bacterial brain abscess. J Clin Neurosci 13(10):979–985
Luder CG, Giraldo-Velasquez M, Sendtner M, Gross U (1999) Toxoplasma gondii in primary rat CNS cells: differential contribution of neurons, astrocytes, and microglial cells for the intracerebral development and stage differentiation. Exp Parasitol 93(1):23–32
Luder CG, Lang C, Giraldo-Velasquez M, Algner M, Gerdes J, Gross U (2003) Toxoplasma gondii inhibits MHC class II expression in neural antigen-presenting cells by down-regulating the class II transactivator CIITA. J Neuroimmunol 134(1–2):12–24
Manning SD (2003) Molecular epidemiology of Streptococcus agalactiae (group B Streptococcus). Front Biosci 8:s1–s18
Mathisen GE, Johnson JP (1997) Brain abscess. Clin Infect Dis 25(4):763–779, quiz 780-1
Mausberg AK, Jander S, Reichmann G (2009) Intracerebral granulocyte-macrophage colony-stimulating factor induces functionally competent dendritic cells in the mouse brain. Glia 57:1341–1350
McGilvray ID, Serghides L, Kapus A, Rotstein OD, Kain KC (2000) Nonopsonic monocyte/macrophage phagocytosis of Plasmodium falciparum-parasitized erythrocytes: a role for CD36 in malarial clearance. Blood 96(9):3231–3240
McKimmie CS, Roy D, Forster T, Fazakerley JK (2006) Innate immune response gene expression profiles of N9 microglia are pathogen-type specific. J Neuroimmunol 175(1–2):128–141
Medana IM, Hunt NH, Chan-Ling T (1997) Early activation of microglia in the pathogenesis of fatal murine cerebral malaria. Glia 19(2):91–103
Medana IM, Chan-Ling T, Hunt NH (2000) Reactive changes of retinal microglia during fatal murine cerebral malaria: effects of dexamethasone and experimental permeabilization of the blood–brain barrier. Am J Pathol 156(3):1055–1065
Miklossy J, Kasas S, Zurn AD, McCall S, Yu S, McGeer PL (2008) Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis. J Neuroinflammation 5:40
Montoya JG, Liesenfeld O (2004) Toxoplasmosis. Lancet 363(9425):1965–1976
Mukhopadhyay S, Herre J, Brown GD, Gordon S (2004) The potential for Toll-like receptors to collaborate with other innate immune receptors. Immunology 112(4):521–530
Murray HW, Rubin BY, Masur H, Roberts RB (1984) Impaired production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome. N Engl J Med 310(14):883–889
Nau R, Bruck W (2002) Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. Trends Neurosci 25(1):38–45
Nichols JR, Aldrich AL, Mariani MM, Vidlak D, Esen N, Kielian T (2009) TLR2 deficiency leads to increased Th17 infiltrates in experimental brain abscesses. J Immunol 182(11):7119–7130
O'Neill LA, Bowie AG (2007) The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 7(5):353–364
Pachner AR, Gelderblom H, Cadavid D (2001) The rhesus model of Lyme neuroborreliosis. Immunol Rev 183:186–204
Pashenkov M, Teleshova N, Kouwenhoven M, Smirnova T, Jin YP, Kostulas V, Huang YM, Pinegin B, Boiko A, Link H (2002) Recruitment of dendritic cells to the cerebrospinal fluid in bacterial neuroinfections. J Neuroimmunol 122(1–2):106–116
Patel SN, Serghides L, Smith TG, Febbraio M, Silverstein RL, Kurtz TW, Pravenec M, Kain KC (2004) CD36 mediates the phagocytosis of Plasmodium falciparum-infected erythrocytes by rodent macrophages. J Infect Dis 189(2):204–213
Peppoloni S, Colombari B, Neglia R, Quaglino D, Iannelli F, Oggioni MR, Pozzi G, Blasi E (2006) The lack of Pneumococcal surface protein C (PspC) increases the susceptibility of Streptococcus pneumoniae to the killing by microglia. Med Microbiol Immunol 195(1):21–28
Peterson PK, Hu S, Anderson WR, Chao CC (1994) Nitric oxide production and neurotoxicity mediated by activated microglia from human versus mouse brain. J Infect Dis 170(2):457–460
Pfister HW, Rupprecht TA (2006) Clinical aspects of neuroborreliosis and post-Lyme disease syndrome in adult patients. Int J Med Microbiol 296(Suppl 40):11–16
Pfister HW, Feiden W, Einhaupl KM (1993) Spectrum of complications during bacterial meningitis in adults. Results of a prospective clinical study. Arch Neurol 50(6):575–581
Pfister HW, Wilske B, Weber K (1994) Lyme borreliosis: basic science and clinical aspects. Lancet 343(8904):1013–1016
Ponomarev ED, Novikova M, Maresz K, Shriver LP, Dittel BN (2005) Development of a culture system that supports adult microglial cell proliferation and maintenance in the resting state. J Immunol Methods 300(1–2):32–46
Prasad KN, Mishra AM, Gupta D, Husain N, Husain M, Gupta RK (2006) Analysis of microbial etiology and mortality in patients with brain abscess. J Infect 53(4):221–227
Prinz M, Kann O, Draheim HJ, Schumann RR, Kettenmann H, Weber JR, Hanisch UK (1999) Microglial activation by components of gram-positive and -negative bacteria: distinct and common routes to the induction of ion channels and cytokines. J Neuropathol Exp Neurol 58(10):1078–1089
Ramesh G, Borda JT, Dufour J, Kaushal D, Ramamoorthy R, Lackner AA, Philipp MT (2008) Interaction of the Lyme disease spirochete Borrelia burgdorferi with brain parenchyma elicits inflammatory mediators from glial cells as well as glial and neuronal apoptosis. Am J Pathol 173(5):1415–1427
Rasley A, Anguita J, Marriott I (2002) Borrelia burgdorferi induces inflammatory mediator production by murine microglia. J Neuroimmunol 130(1–2):22–31
Rasley A, Tranguch SL, Rati DM, Marriott I (2006) Murine glia express the immunosuppressive cytokine, interleukin-10, following exposure to Borrelia burgdorferi or Neisseria meningitidis. Glia 53(6):583–592
Rock RB, Gekker G, Hu S, Sheng WS, Cheeran M, Lokensgard JR, Peterson PK (2004) Role of microglia in central nervous system infections. Clin Microbiol Rev 17(4):942–964, table of contents
Rozenfeld C, Martinez R, Figueiredo RT, Bozza MT, Lima FR, Pires AL, Silva PM, Bonomo A, Lannes-Vieira J, De Souza W et al (2003) Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration. Infect Immun 71(4):2047–2057
Rupprecht TA, Koedel U, Fingerle V, Pfister HW (2008) The pathogenesis of lyme neuroborreliosis: from infection to inflammation. Mol Med 14(3–4):205–212
Saccente M (2008) Central nervous system histoplasmosis. Curr Treat Options Neurol 10(3):161–167
Scheld WM, Koedel U, Nathan B, Pfister HW (2002) Pathophysiology of bacterial meningitis: mechanism(s) of neuronal injury. J Infect Dis 186(Suppl 2):S225–S233
Schluesener HJ, Kremsner PG, Meyermann R (1998) Widespread expression of MRP8 and MRP14 in human cerebral malaria by microglial cells. Acta Neuropathol 96(6):575–580
Schluter D, Hein A, Dorries R, Deckert-Schluter M (1995) Different subsets of T cells in conjunction with natural killer cells, macrophages, and activated microglia participate in the intracerebral immune response to Toxoplasma gondii in athymic nude and immunocompetent rats. Am J Pathol 146(4):999–1007
Schluter D, Kaefer N, Hof H, Wiestler OD, Deckert-Schluter M (1997) Expression pattern and cellular origin of cytokines in the normal and Toxoplasma gondii-infected murine brain. Am J Pathol 150(3):1021–1035
Schluter D, Kwok LY, Lutjen S, Soltek S, Hoffmann S, Korner H, Deckert M (2003) Both lymphotoxin-alpha and TNF are crucial for control of Toxoplasma gondii in the central nervous system. J Immunol 170(12):6172–6182
Schneemann M, Schoedon G, Hofer S, Blau N, Guerrero L, Schaffner A (1993) Nitric oxide synthase is not a constituent of the antimicrobial armature of human mononuclear phagocytes. J Infect Dis 167(6):1358–1363
Schofield L, Grau GE (2005) Immunological processes in malaria pathogenesis. Nat Rev Immunol 5(9):722–735
Sedgwick JD, Schwender S, Imrich H, Dorries R, Butcher GW, ter Meulen V (1991) Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc Natl Acad Sci USA 88(16):7438–7442
Shimoda M, Jones VC, Kobayashi M, Suzuki F (2006) Microglial cells from psychologically stressed mice as an accelerator of cerebral cryptococcosis. Immunol Cell Biol 84(6):551–556
Somand D, Meurer W (2009) Central nervous system infections. Emerg Med Clin North Am 27(1):89–100, ix
Sowa G, Gekker G, Lipovsky MM, Hu S, Chao CC, Molitor TW, Peterson PK (1997) Inhibition of swine microglial cell phagocytosis of Cryptococcus neoformans by femtomolar concentrations of morphine. Biochem Pharmacol 53(6):823–828
Strack A, Schluter D, Asensio VC, Campbell IL, Deckert M (2002) Regulation of the kinetics of intracerebral chemokine gene expression in murine Toxoplasma encephalitis: impact of host genetic factors. Glia 40(3):372–377
Szklarczyk A, Stins M, Milward EA, Ryu H, Fitzsimmons C, Sullivan D, Conant K (2007) Glial activation and matrix metalloproteinase release in cerebral malaria. J Neurovirol 13(1):2–10
Tambuyzer BR, Ponsaerts P, Nouwen EJ (2009) Microglia: gatekeepers of central nervous system immunology. J Leukoc Biol 85(3):352–370
Togbe D, Schofield L, Grau GE, Schnyder B, Boissay V, Charron S, Rose S, Beutler B, Quesniaux VF, Ryffel B (2007) Murine cerebral malaria development is independent of toll-like receptor signaling. Am J Pathol 170(5):1640–1648
Townsend GC, Scheld WM (1998) Infections of the central nervous system. Adv Intern Med 43:403–447
Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, Tocker J, Peschon J (2006) Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol 177(1):36–39
Trajkovic V, Stosic-Grujicic S, Samardzic T, Markovic M, Miljkovic D, Ramic Z, Mostarica Stojkovic M (2001) Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent astrocytes. J Neuroimmunol 119(2):183–191
Underhill DM, Gantner B (2004) Integration of Toll-like receptor and phagocytic signaling for tailored immunity. Microbes Infect 6(15):1368–1373
Wennekamp J, Henneke P (2008) Induction and termination of inflammatory signaling in group B streptococcal sepsis. Immunol Rev 225:114–127
Wesche H, Henzel WJ, Shillinglaw W, Li S, Cao Z (1997) MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7(6):837–847
Zhou Q, Gault RA, Kozel TR, Murphy WJ (2007) Protection from direct cerebral cryptococcus infection by interferon-gamma-dependent activation of microglial cells. J Immunol 178(9):5753–5761
Acknowledgments
This work was supported by the NIH National Institute of Neurological Disorders and Stroke (NINDS; RO1s NS040740, NS055385, and NS053487) to T.K.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mariani, M.M., Kielian, T. Microglia in Infectious Diseases of the Central Nervous System. J Neuroimmune Pharmacol 4, 448–461 (2009). https://doi.org/10.1007/s11481-009-9170-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11481-009-9170-6