Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid

Journal of Inflammation

Research

Yong Jun Goh¹  Kurt Selle¹  Todd Klaenhammer¹  Mansour Mohamadzadeh²  Mojgan Zadeh²  Jennifer L Owen²  Mohammad W Khan³ 

[1] Department of Food, Bioprocessing & Nutrition Sciences, N.C. State University, Raleigh, NC, USA;Department of Infectious Diseases and Pathology, Emerging Pathogens Institute, and Cancer Genetic Institute, University of Florida, Gainesville, FL, USA;Northwestern University, Feinberg School of Medicine, Chicago, IL, USA;

关键词: Dendritic cells;    Dextran sulfate sodium;    Inflammatory bowel disease;    Lipoteichoic acid;    Toll-like receptor 2;   

DOI  :  10.1186/1476-9255-9-7

 received in 2011-11-28, accepted in 2012-03-16,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsTo 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 s urface l ayer p rotein (Slp) genes encoding SlpB and SlpX were deleted resulting in a SlpB- and SlpX- mutant that continued to express SlpA (assigned as NCK2031).ResultsOur 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.ConclusionsThese findings suggest that directed alteration of two of the L. acidophilus NCFM-Slps did not ameliorate LTA-induced pro-inflammatory signals and subsequent colitis.

【 授权许可】

Unknown   
© Zadeh et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.