Skip to main content

Advertisement

Log in

Microglia in Infectious Diseases of the Central Nervous System

  • Invited Review
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

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

    Article  PubMed  CAS  Google Scholar 

  • Aguirre K, Miller S (2002) MHC class II-positive perivascular microglial cells mediate resistance to Cryptococcus neoformans brain infection. Glia 39(2):184–188

    Article  PubMed  Google Scholar 

  • Akira S (2006) TLR signaling. Curr Top Microbiol Immunol 311:1–16

    Article  PubMed  CAS  Google Scholar 

  • Aloisi F (2001) Immune function of microglia. Glia 36(2):165–179

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Carson MJ, Reilly CR, Sutcliffe JG, Lo D (1998) Mature microglia resemble immature antigen-presenting cells. Glia 22(1):72–85

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Deininger MH, Kremsner PG, Meyermann R, Schluesener H (2002) Macrophages/microglial cells in patients with cerebral malaria. Eur Cytokine Netw 13(2):173–185

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Engwerda C, Belnoue E, Gruner AC, Renia L (2005) Experimental models of cerebral malaria. Curr Top Microbiol Immunol 297:103–143

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Fischer HG, Reichmann G (2001) Brain dendritic cells and macrophages/microglia in central nervous system inflammation. J Immunol 166(4):2717–2726

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Galiza EP, Heath PT (2009) Improving the outcome of neonatal meningitis. Curr Opin Infect Dis 22(3):229–234

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • Hanisch UK (2002) Microglia as a source and target of cytokines. Glia 40(2):140–155

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Hengge UR, Tannapfel A, Tyring SK, Erbel R, Arendt G, Ruzicka T (2003) Lyme borreliosis. Lancet Infect Dis 3(8):489–500

    Article  PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Idro R, Jenkins NE, Newton CR (2005) Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol 4(12):827–840

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Kielian T (2004) Immunopathogenesis of brain abscess. J Neuroinflammation 1(1):16

    Article  PubMed  CAS  Google Scholar 

  • Kielian T (2006) Toll-like receptors in central nervous system glial inflammation and homeostasis. J Neurosci Res 83(5):711–730

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Kim K, Weiss LM (2008) Toxoplasma: the next 100 years. Microbes Infect 10(9):978–984

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Koedel U, Scheld WM, Pfister HW (2002) Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis 2(12):721–736

    Article  PubMed  Google Scholar 

  • Larsen PH, Holm TH, Owens T (2007) Toll-like receptors in brain development and homeostasis. Sci STKE 2007(402):pe47

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Lu CH, Chang WN, Lui CC (2006) Strategies for the management of bacterial brain abscess. J Clin Neurosci 13(10):979–985

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Manning SD (2003) Molecular epidemiology of Streptococcus agalactiae (group B Streptococcus). Front Biosci 8:s1–s18

    Article  PubMed  CAS  Google Scholar 

  • Mathisen GE, Johnson JP (1997) Brain abscess. Clin Infect Dis 25(4):763–779, quiz 780-1

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Montoya JG, Liesenfeld O (2004) Toxoplasmosis. Lancet 363(9425):1965–1976

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Nau R, Bruck W (2002) Neuronal injury in bacterial meningitis: mechanisms and implications for therapy. Trends Neurosci 25(1):38–45

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Pachner AR, Gelderblom H, Cadavid D (2001) The rhesus model of Lyme neuroborreliosis. Immunol Rev 183:186–204

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Pfister HW, Wilske B, Weber K (1994) Lyme borreliosis: basic science and clinical aspects. Lancet 343(8904):1013–1016

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Rasley A, Anguita J, Marriott I (2002) Borrelia burgdorferi induces inflammatory mediator production by murine microglia. J Neuroimmunol 130(1–2):22–31

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Saccente M (2008) Central nervous system histoplasmosis. Curr Treat Options Neurol 10(3):161–167

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Schofield L, Grau GE (2005) Immunological processes in malaria pathogenesis. Nat Rev Immunol 5(9):722–735

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Somand D, Meurer W (2009) Central nervous system infections. Emerg Med Clin North Am 27(1):89–100, ix

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Tambuyzer BR, Ponsaerts P, Nouwen EJ (2009) Microglia: gatekeepers of central nervous system immunology. J Leukoc Biol 85(3):352–370

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Townsend GC, Scheld WM (1998) Infections of the central nervous system. Adv Intern Med 43:403–447

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Underhill DM, Gantner B (2004) Integration of Toll-like receptor and phagocytic signaling for tailored immunity. Microbes Infect 6(15):1368–1373

    Article  PubMed  CAS  Google Scholar 

  • Wennekamp J, Henneke P (2008) Induction and termination of inflammatory signaling in group B streptococcal sepsis. Immunol Rev 225:114–127

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

Download references

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

Authors

Corresponding author

Correspondence to Tammy Kielian.

Rights and permissions

Reprints 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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11481-009-9170-6

Keywords

Navigation