title: Antimicrobial peptide response to group B Streptococcus in human extraplacental membranes in culture.
abstract: OBJECTIVE
  Streptococcus agalactiae (GBS) is an important cause of chorioamnionitis. This study characterizes GBS colonization and stimulation of antimicrobial responses in human extraplacental membranes using an ex vivo transwell two-compartment system of full-thickness membranes and live GBS.
  
  
  METHODS
  Human extraplacental membranes were affixed to transwell frames (without synthetic membranes). Live GBS was added to the decidual side of membranes in transwell cultures, and cocultures were incubated for 4, 8 and 24 h. GBS recovery from homogenized membranes and culture medium was determined by enumerating colony forming units (CFU) on blood agar. Antimicrobial peptide expression was identified using immunohistochemistry and ELISA. GBS killing by HBDs was assessed in vitro by incubating GBS with different human beta defensins (HBDs) for 3 h, then enumerating CFU.
  
  
  RESULTS
  GBS recovery from membranes markedly decreased over time (P < 0.05). The antimicrobial peptides HBD-1, HBD-2, HBD-3, and lactoferrin were expressed in both GBS-exposed and non-exposed tissues. Notably, a pattern of localized increased HBD-2 in the amnion of GBS-infected tissue was observed. Moreover, GBS-treated membranes released increased amounts of HBD-2 into the amniotic and decidual compartments of the transwell cultures after 24 h (P < 0.05). In bacterial cultures, HBD-2 decreased GBS viability in a concentration-dependent manner (P < 0.05).
  
  
  CONCLUSIONS
  Innate immune responses in ex vivo human extraplacental membranes suppress GBS growth. HBD-2 was implicated in this GBS suppression with evidence of signal transduction across the tissue. Antimicrobial peptides may be important for innate immune defense against intrauterine GBS infections during pregnancy.
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2029, USA. boldenow@umich.edu
authors.forename: E
authors.initials: E
authors.lastname: Boldenow
authors.forename: S
authors.initials: S
authors.lastname: Jones
authors.forename: R W
authors.initials: RW
authors.lastname: Lieberman
authors.forename: M C
authors.initials: MC
authors.lastname: Chames
authors.forename: D M
authors.initials: DM
authors.lastname: Aronoff
authors.forename: C
authors.initials: C
authors.lastname: Xi
authors.forename: R
authors.initials: R
authors.lastname: Loch-Caruso
mesh_terms: D000650:Amnion / Q000737:chemistry / Q000276:immunology / Q000382:microbiology*; D000890:Anti-Infective Agents / Q000032:analysis* / Q000378:metabolism; D002823:Chorion / Q000276:immunology / Q000382:microbiology; D003656:Decidua / Q000276:immunology / Q000382:microbiology*; D005260:Female; D006801:Humans; D011247:Pregnancy; D015398:Signal Transduction; D013290:Streptococcal Infections / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D046509:Tissue Culture Techniques; D023083:beta-Defensins / Q000032:analysis*
chemical_list: D000890:Anti-Infective Agents; C406407:DEFB1 protein, human; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D023083:beta-Defensins
references.citation: Placenta. 2007 Feb-Mar;28(2-3):161-9
references.pmid: 16513165
references.citation: Wound Repair Regen. 2010 Jul-Aug;18(4):368-77
references.pmid: 20636551
references.citation: Biol Reprod. 2004 Oct;71(4):1296-302
references.pmid: 15201199
references.citation: Reprod Sci. 2010 Dec;17(12):1120-9
references.pmid: 20861394
references.citation: J Clin Invest. 1998 Apr 15;101(8):1633-42
references.pmid: 9541493
references.citation: Placenta. 2007 Nov-Dec;28(11-12):1099-106
references.pmid: 17664005
references.citation: J Immunol. 2008 Jun 15;180(12):8222-30
references.pmid: 18523288
references.citation: N Engl J Med. 2000 May 18;342(20):1500-7
references.pmid: 10816189
references.citation: Reprod Biol Endocrinol. 2010 Dec 01;8:146
references.pmid: 21122132
references.citation: J Dermatol Sci. 2005 Nov;40(2):123-32
references.pmid: 15963694
references.citation: Am J Obstet Gynecol. 1979 Aug 1;134(7):833-45
references.pmid: 380345
references.citation: Eur J Obstet Gynecol Reprod Biol. 2001 Feb;94(2):224-9
references.pmid: 11165729
references.citation: MMWR Recomm Rep. 2010 Nov 19;59(RR-10):1-36
references.pmid: 21088663
references.citation: Eur J Obstet Gynecol Reprod Biol. 1999 Apr;83(2):165-9
references.pmid: 10391527
references.citation: J Matern Fetal Neonatal Med. 2012 Apr;25(4):358-63
references.pmid: 21631237
references.citation: Infect Immun. 1998 Oct;66(10):4932-41
references.pmid: 9746599
references.citation: Pediatr Infect Dis J. 2008 Dec;27(12):1057-64
references.pmid: 18989238
references.citation: Infect Dis Obstet Gynecol. 2000;8(5-6):220-7
references.pmid: 11220481
references.citation: Curr Opin Ophthalmol. 2005 Aug;16(4):233-40
references.pmid: 16000896
references.citation: Am J Obstet Gynecol. 1984 Apr 1;148(7):915-28
references.pmid: 6424476
references.citation: J Immunol. 2005 Feb 1;174(3):1608-15
references.pmid: 15661923
references.citation: Infect Immun. 1998 Sep;66(9):4222-8
references.pmid: 9712771
references.citation: Reprod Biol Endocrinol. 2009 Oct 26;7:117
references.pmid: 19857262
references.citation: J Exp Med. 1975 Jul 1;142(1):165-79
references.pmid: 1097573
references.citation: Reprod Biol Endocrinol. 2007 Dec 13;5:46
references.pmid: 18078521
references.citation: Am J Obstet Gynecol. 1991 Oct;165(4 Pt 1):955-61
references.pmid: 1951562
references.citation: Am J Obstet Gynecol. 1996 Jun;174(6):1725-31; discussion 1731-3
references.pmid: 8678133