title: Evidence of involvement of the mannose receptor in the internalization of Streptococcus pneumoniae by Schwann cells.
abstract: BACKGROUND
  The ability of S. pneumoniae to generate infections depends on the restrictions imposed by the host's immunity, in order to prevent the bacterium from spreading from the nasopharynx to other tissues, such as the brain. Some authors claim that strains of S. pneumoniae, which fail to survive in the bloodstream, can enter the brain directly from the nasal cavity by axonal transport through the olfactory and/or trigeminal nerves. However, from the immunological point of view, glial cells are far more responsive to bacterial infections than are neurons. This hypothesis is consistent with several recent reports showing that bacteria can infect glial cells from the olfactory bulb and trigeminal ganglia. Since our group previously demonstrated that Schwann cells (SCs) express a functional and appropriately regulated mannose receptor (MR), we decided to test whether SCs are involved in the internalization of S. pneumoniae via MR.
  
  
  RESULTS
  Immediately after the interaction step, as well as 3 h later, the percentage of association was approximately 56.5%, decreasing to 47.2% and 40.8% after 12 and 24 h, respectively. Competition assays by adding a 100-fold excess of mannan prior to the S. pneumoniae infection reduced the number of infected cells at 3 and 24 h. A cytochemistry assay with Man/BSA-FITC binding was performed in order to verify a possible overlap between mannosylated ligands and internalized bacteria. Incubation of the SCs with Man/BSA-FITC resulted in a large number of intracellular S. pneumoniae, with nearly complete loss of the capsule. Moreover, the anti-pneumococcal antiserum staining colocalized with the internalized man/BSA-FITC, suggesting that both markers are present within the same endocytic compartment of the SC.
  
  
  CONCLUSIONS
  Our data offer novel evidence that SCs could be essential for pneumococcal cells to escape phagocytosis and killing by innate immune cells. On the other hand, the results also support the idea that SCs are immunocompetent cells of the PNS that can mediate an efficient immune response against pathogens via MR.
authors.forename: Hugo
authors.initials: H
authors.lastname: Macedo-Ramos
authors.forename: Andre F
authors.initials: AF
authors.lastname: Batista
authors.forename: Alvaro
authors.initials: A
authors.lastname: Carrier-Ruiz
authors.forename: Lucineia
authors.initials: L
authors.lastname: Alves
authors.forename: Silvana
authors.initials: S
authors.lastname: Allodi
authors.forename: Victor T
authors.initials: VT
authors.lastname: Ribeiro-Resende
authors.forename: Lucia M
authors.initials: LM
authors.lastname: Teixeira
authors.affiliation: Faculdade de Medicina, Centro de Cirurgia Experimental, Laboratório Translacional em Fisiologia Molecular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. wagner.baetas@ufrj.br.
authors.forename: Wagner
authors.initials: W
authors.lastname: Baetas-da-Cruz
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis; D054884:Host-Pathogen Interactions; D037181:Lectins, C-Type / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012583:Schwann Cells / Q000276:immunology* / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface
references.citation: Brain Res. 2012 May 3;1452:173-84
references.pmid: 22459039
references.citation: Appl Environ Microbiol. 1997 Jun;63(6):2421-31
references.pmid: 9172364
references.citation: FEMS Microbiol Lett. 2004 Sep 15;238(2):429-37
references.pmid: 15358430
references.citation: J Neurosci. 1991 Aug;11(8):2433-42
references.pmid: 1869923
references.citation: J Infect Dis. 1985 Jul;152(1):4-13
references.pmid: 3874252
references.citation: J Immunol. 2011 Sep 1;187(5):2548-58
references.pmid: 21813774
references.citation: J Leukoc Biol. 2012 Dec;92(6):1177-86
references.pmid: 22966131
references.citation: J Craniofac Surg. 2008 Nov;19(6):1542-8
references.pmid: 19098547
references.citation: J Mol Med (Berl). 2010 Feb;88(2):103-7
references.pmid: 20162252
references.citation: Glia. 2010 Nov 1;58(14):1701-9
references.pmid: 20578041
references.citation: Int J Biochem Cell Biol. 2001 Jul;33(7):637-68
references.pmid: 11390274
references.citation: Neurosci Res. 2011 Apr;69(4):308-13
references.pmid: 21192991
references.citation: J Immunol. 2009 Aug 1;183(3):1952-63
references.pmid: 19570831
references.citation: Infect Immun. 2001 Jan;69(1):602-6
references.pmid: 11119562
references.citation: Br J Dermatol. 2008 Mar;158(3):631-3
references.pmid: 18070200
references.citation: Nat Struct Mol Biol. 2010 May;17(5):576-81
references.pmid: 20400948
references.citation: J Infect Dis. 1997 Dec;176 Suppl 2:S173-9
references.pmid: 9396706
references.citation: FEMS Immunol Med Microbiol. 2012 Dec;66(3):427-35
references.pmid: 23163874
references.citation: Infect Immun. 2003 Mar;71(3):1427-33
references.pmid: 12595460
references.citation: Clin Infect Dis. 2008 Jan 1;46(1):e1-7
references.pmid: 18171202
references.citation: Int Rev Cytol. 2003;226:321-42
references.pmid: 12921240
references.citation: Neurobiol Dis. 2013 Jul;55:95-103
references.pmid: 23523637
references.citation: J Exp Med. 1999 Jun 21;189(12):1961-72
references.pmid: 10377192
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14363-7
references.pmid: 14610280
references.citation: J Peripher Nerv Syst. 2009 Jun;14(2):84-92
references.pmid: 19691530
references.citation: Histol Histopathol. 2009 Aug;24(8):1029-34
references.pmid: 19554510
references.citation: Int J Infect Dis. 2009 Sep;13(5):e323-4
references.pmid: 19157949
references.citation: J Biol Chem. 2002 Nov 1;277(44):41613-23
references.pmid: 12196537
references.citation: Cell. 1997 Oct 31;91(3):295-8
references.pmid: 9363937
references.citation: Glia. 2007 Jul;55(9):905-16
references.pmid: 17427933
references.citation: Nat Rev Microbiol. 2007 Mar;5(3):219-29
references.pmid: 17277796
references.citation: Int J Infect Dis. 2006 Mar;10(2):110-5
references.pmid: 16310395
references.citation: J Neurosci Res. 1994 Feb 15;37(3):415-32
references.pmid: 7513766
references.citation: J Neuroinflammation. 2012 May 29;9:109
references.pmid: 22642871
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8710-5
references.pmid: 15928084
references.citation: Glia. 2003 Apr 1;42(1):89-100
references.pmid: 12594740
references.citation: J Neurosci Res. 2013 Dec;91(12):1572-80
references.pmid: 24105692
references.citation: J Neurosci Res. 1999 Nov 1;58(3):387-95
references.pmid: 10518112
references.citation: Cell Tissue Res. 2001 Mar;303(3):307-17
references.pmid: 11320646
references.citation: Glycobiology. 2011 Sep;21(9):1121-4
references.pmid: 21932452
references.citation: Glia. 2010 Feb;58(3):367-76
references.pmid: 19780198
references.citation: Infect Immun. 2010 Feb;78(2):865-71
references.pmid: 19933834
references.citation: PLoS One. 2013 Jul 16;8(7):e68408
references.pmid: 23874613
references.citation: Neurosci Lett. 2013 Feb 28;539:65-70
references.pmid: 23415759