title: Toll-like receptor stimulation increases phagocytosis of Cryptococcus neoformans by microglial cells.
abstract: BACKGROUND
  Toll-Like receptors (TLRs) belong to the family of pattern-recognition receptors with a crucial function of recognising pathogen-associated molecular patterns (PAMPs). Cryptococcal meningitis is a potentially fatal disease with a high mortality and risk of neurological sequelae.
  
  
  METHODS
  We studied the ability of microglial cells to increase the phagocytosis of cryptococci after stimulation with agonists of TLR1/2, TLR3, TLR4 and TLR9.
  
  
  RESULTS
  Stimulation of murine microglial cells with these TLR agonists for 24 h increased the phagocytosis of encapsulated Cryptococcus neoformans. Stimulation increased the release of TNF-α, CXCL1 (KC), IL-6, IL-10 and MIP-2, which indicated the activation of microglial cells. Unstimulated and TLR agonist-stimulated MyD88-deficient cells showed a reduced ability to phagocytose cryptococci compared to their wild-type counterpart. Intracellular killing of cryptococci was also increased in TLR-stimulated cells compared to unstimulated microglial cells.
  
  
  CONCLUSIONS
  Our observation suggests that stimulation of microglial cells by TLR agonists can increase the resistance of the brain against CNS infections caused by Cryptococcus neoformans. This may be of interest when an immunocompromised patient is unable to eliminate Cryptococcus neoformans despite antifungal therapy.
authors.affiliation: Institute of Neuropathology, University Medical Center, Göttingen, Germany. s.redlich77@web.de
authors.forename: Sandra
authors.initials: S
authors.lastname: Redlich
authors.forename: Sandra
authors.initials: S
authors.lastname: Ribes
authors.forename: Sandra
authors.initials: S
authors.lastname: Schütze
authors.forename: Helmut
authors.initials: H
authors.lastname: Eiffert
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D055666:Lipopeptides / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D011070:Poly I-C / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D018925:Chemokines; D016207:Cytokines; D055666:Lipopeptides; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C508075:Pam(3)CSK(4) peptide; D051193:Toll-Like Receptors; D011070:Poly I-C