title: Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid.
abstract: BACKGROUND
  The cellular and molecular mechanisms of inflammatory bowel disease are not fully understood; however, data indicate that uncontrolled chronic inflammation induced by bacterial gene products, including lipoteichoic acid (LTA), may trigger colonic inflammation resulting in disease pathogenesis. LTA is a constituent glycolipid of Gram-positive bacteria that shares many inflammatory properties with lipopolysaccharide and plays a critical role in the pathogenesis of severe inflammatory responses via Toll-like receptor 2. Accordingly, we elucidate the role of LTA in immune stimulation and induced colitis in vivo.
  
  
  METHODS
  To better understand the molecular mechanisms utilized by the intestinal microbiota and their gene products to induce or subvert inflammation, specifically the effect(s) of altered surface layer protein expression on the LTA-mediated pro-inflammatory response, the Lactobacillus acidophilus surface layer protein (Slp) genes encoding SlpB and SlpX were deleted resulting in a SlpB- and SlpX- mutant that continued to express SlpA (assigned as NCK2031).
  
  
  RESULTS
  Our data show profound activation of dendritic cells by NCK2031, wild-type L. acidophilus (NCK56), and purified Staphylococcus aureus-LTA. In contrary to the LTA-deficient strain NCK2025, the LTA-expressing strains NCK2031 and NCK56, as well as S. aureus-LTA, induce pro-inflammatory innate and T cell immune responses in vivo. Additionally, neither NCK2031 nor S. aureus-LTA supplemented in drinking water protected mice from DSS-colitis, but instead, induced significant intestinal inflammation resulting in severe colitis and tissue destruction.
  
  
  CONCLUSIONS
  These findings suggest that directed alteration of two of the L. acidophilus NCFM-Slps did not ameliorate LTA-induced pro-inflammatory signals and subsequent colitis.
authors.affiliation: Department of Infectious Diseases and Pathology, Emerging Pathogens Institute, and Cancer Genetic Institute, University of Florida, Gainesville, FL, USA. m.zadeh@ufl.edu.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Zadeh
authors.forename: Mohammad W
authors.initials: MW
authors.lastname: Khan
authors.forename: Yong Jun
authors.initials: YJ
authors.lastname: Goh
authors.forename: Kurt
authors.initials: K
authors.lastname: Selle
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Owen
authors.forename: Todd
authors.initials: T
authors.lastname: Klaenhammer
authors.forename: Mansour
authors.initials: M
authors.lastname: Mohamadzadeh